ClinVar Genomic variation as it relates to human health
NM_000478.6(ALPL):c.299_300insT (p.Tyr101fs)
criteria provided, single submitter. Learn more about how ClinVar calculates review status.
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000478.6(ALPL):c.299_300insT (p.Tyr101fs)
Variation ID: 2762389 Accession: VCV002762389.2
- Type and length
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Insertion, 1 bp
- Location
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Cytogenetic: 1p36.12 1: 21563111-21563112 (GRCh38) [ NCBI UCSC ] 1: 21889604-21889605 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Feb 14, 2024 Mar 4, 2025 Sep 21, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000478.6:c.299_300insT MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000469.3:p.Tyr101fs frameshift NM_001127501.4:c.134_135insT NP_001120973.2:p.Tyr46fs frameshift NM_001177520.3:c.68_69insT NP_001170991.1:p.Tyr24fs frameshift NM_001369803.2:c.299_300insT NP_001356732.1:p.Tyr101fs frameshift NM_001369804.2:c.299_300insT NP_001356733.1:p.Tyr101fs frameshift NM_001369805.2:c.299_300insT NP_001356734.1:p.Tyr101fs frameshift NC_000001.11:g.21563111_21563112insT NC_000001.10:g.21889604_21889605insT NG_008940.1:g.58747_58748insT NG_008940.2:g.59129_59130insT - Protein change
- Y101fs, Y46fs, Y24fs
- Other names
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- Canonical SPDI
- NC_000001.11:21563111::T
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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| HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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| ALPL | - | - |
GRCh38 GRCh37 |
1530 | 1546 | |
Conditions - Germline
| Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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| Pathogenic (1) |
criteria provided, single submitter
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Sep 21, 2023 | RCV003570050.3 |
Submissions - Germline
| Classification
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The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Sep 21, 2023)
C
Contributing to aggregate classification
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criteria provided, single submitter
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not provided |
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004325561.2
First in ClinVar: Feb 14, 2024 Last updated: Mar 04, 2025 |
Comment:
This sequence change creates a premature translational stop signal (p.Tyr101Valfs*9) in the ALPL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALPL are known to be pathogenic (PMID: 3174660, 10679946, 32973344, 33814268). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ALPL-related conditions. For these reasons, this variant has been classified as Pathogenic.
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
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Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Investigation of ALPL variant states and clinical outcomes: An analysis of adults and adolescents with hypophosphatasia treated with asfotase alfa. | Kishnani PS | Molecular genetics and metabolism | 2021 | PMID: 33814268 |
| Hypophosphatasia: a genetic-based nosology and new insights in genotype-phenotype correlation. | Mornet E | European journal of human genetics : EJHG | 2021 | PMID: 32973344 |
| Fifteen new mutations (-195C>T, L-12X, 298-2A>G, T117N, A159T, R229S, 997+2T>A, E274X, A331T, H364R, D389G, 1256delC, R433H, N461I, C472S) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in patients with hypophosphatasia. | Taillandier A | Human mutation | 2000 | PMID: 10679946 |
| A missense mutation in the human liver/bone/kidney alkaline phosphatase gene causing a lethal form of hypophosphatasia. | Weiss MJ | Proceedings of the National Academy of Sciences of the United States of America | 1988 | PMID: 3174660 |
Text-mined citations for rs2545298399 ...
HelpRecord last updated May 19, 2025
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the "most recent submission" reported at the top of this page.