U.S. flag

An official website of the United States government

NM_000478.6(ALPL):c.655A>G (p.Met219Val) AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 4, 2024
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001351724.7

Allele description [Variation Report for NM_000478.6(ALPL):c.655A>G (p.Met219Val)]

NM_000478.6(ALPL):c.655A>G (p.Met219Val)

Gene:
ALPL:alkaline phosphatase, biomineralization associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p36.12
Genomic location:
Preferred name:
NM_000478.6(ALPL):c.655A>G (p.Met219Val)
HGVS:
  • NC_000001.11:g.21568110A>G
  • NG_008940.1:g.63746A>G
  • NM_000478.6:c.655A>GMANE SELECT
  • NM_001127501.4:c.490A>G
  • NM_001177520.3:c.424A>G
  • NM_001369803.2:c.655A>G
  • NM_001369804.2:c.655A>G
  • NM_001369805.2:c.655A>G
  • NP_000469.3:p.Met219Val
  • NP_001120973.2:p.Met164Val
  • NP_001170991.1:p.Met142Val
  • NP_001356732.1:p.Met219Val
  • NP_001356733.1:p.Met219Val
  • NP_001356734.1:p.Met219Val
  • NC_000001.10:g.21894603A>G
Protein change:
M142V
Links:
dbSNP: rs772432010
NCBI 1000 Genomes Browser:
rs772432010
Molecular consequence:
  • NM_000478.6:c.655A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127501.4:c.490A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001177520.3:c.424A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369803.2:c.655A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369804.2:c.655A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369805.2:c.655A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001546218Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Jan 4, 2024)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Characterization of six missense mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in Chinese children with hypophosphatasia.

Yang H, Wang L, Geng J, Yu T, Yao RE, Shen Y, Yin L, Ying D, Huang R, Zhou Y, Chen H, Liu L, Mo X, Shen Y, Fu Q, Yu Y.

Cell Physiol Biochem. 2013;32(3):635-44. doi: 10.1159/000354467. Epub 2013 Sep 10.

PubMed [citation]
PMID:
24022022

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001546218.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 219 of the ALPL protein (p.Met219Val). This variant is present in population databases (rs772432010, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of hypophosphatasia (PMID: 24022022; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1047062). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ALPL protein function with a positive predictive value of 95%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on ALPL function (PMID: 24022022). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024