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NM_000478.6(ALPL):c.335G>C (p.Gly112Ala) AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 13, 2022
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:
RCV001374069.7

Allele description [Variation Report for NM_000478.6(ALPL):c.335G>C (p.Gly112Ala)]

NM_000478.6(ALPL):c.335G>C (p.Gly112Ala)

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.335G>C (p.Gly112Ala)
HGVS:
  • NC_000001.11:g.21563147G>C
  • NG_008940.1:g.58783G>C
  • NM_000478.6:c.335G>CMANE SELECT
  • NM_001127501.4:c.170G>C
  • NM_001177520.3:c.104G>C
  • NM_001369803.2:c.335G>C
  • NM_001369804.2:c.335G>C
  • NM_001369805.2:c.335G>C
  • NP_000469.3:p.Gly112Ala
  • NP_001120973.2:p.Gly57Ala
  • NP_001170991.1:p.Gly35Ala
  • NP_001356732.1:p.Gly112Ala
  • NP_001356733.1:p.Gly112Ala
  • NP_001356734.1:p.Gly112Ala
  • NC_000001.10:g.21889640G>C
Protein change:
G112A
Links:
dbSNP: rs2148158307
NCBI 1000 Genomes Browser:
rs2148158307
Molecular consequence:
  • NM_000478.6:c.335G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127501.4:c.170G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001177520.3:c.104G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369803.2:c.335G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369804.2:c.335G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369805.2:c.335G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001570837Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jun 13, 2022) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Positive maternal serum triple test screening in severe early onset hypophosphatasia.

Witters I, Moerman P, Mornet E, Fryns JP.

Prenat Diagn. 2004 Jul;24(7):494-7.

PubMed [citation]
PMID:
15300736

First Korean Case of Infantile Hypophosphatasia with Novel Mutation in ALPL and Literature Review.

Park EG, Cho SY, Lee J, Kim J, Cho H, Kim J, Huh R, Ki CS, Kim OH, Jin DK.

Ann Clin Lab Sci. 2016 May;46(3):302-7. Review.

PubMed [citation]
PMID:
27312557
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001570837.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

ClinVar contains an entry for this variant (Variation ID: 1064140). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly112 amino acid residue in ALPL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15300736, 27312557, 28127875, 32160374). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. This missense change has been observed in individual(s) with hypophosphatemia (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 112 of the ALPL protein (p.Gly112Ala).

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

Last Updated: Sep 29, 2024