NM_000169.3(GLA):c.926C>T (p.Ala309Val) AND not provided

Clinical significance:Uncertain significance (Last evaluated: Sep 16, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000414172.2

Allele description [Variation Report for NM_000169.3(GLA):c.926C>T (p.Ala309Val)]

NM_000169.3(GLA):c.926C>T (p.Ala309Val)

Genes:
RPL36A-HNRNPH2:RPL36A-HNRNPH2 readthrough [Gene - HGNC]
GLA:galactosidase alpha [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq22.1
Genomic location:
Preferred name:
NM_000169.3(GLA):c.926C>T (p.Ala309Val)
HGVS:
  • NC_000023.11:g.101398443G>A
  • NG_007119.1:g.14521C>T
  • NM_000169.2:c.926C>T
  • NM_000169.3:c.926C>TMANE SELECT
  • NM_001199973.2:c.300+2986G>A
  • NM_001199974.2:c.177+6621G>A
  • NP_000160.1:p.Ala309Val
  • NP_000160.1:p.Ala309Val
  • LRG_672t1:c.926C>T
  • LRG_672:g.14521C>T
  • LRG_672p1:p.Ala309Val
  • NC_000023.10:g.100653431G>A
  • NR_164783.1:n.1005C>T
  • P06280:p.Ala309Val
  • p.A309V
Protein change:
A309V
Links:
UniProtKB: P06280#VAR_077406; dbSNP: rs869312155
NCBI 1000 Genomes Browser:
rs869312155
Molecular consequence:
  • NM_001199973.2:c.300+2986G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001199974.2:c.177+6621G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000169.2:c.926C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000169.3:c.926C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_164783.1:n.1005C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Functional consequence:
effect on protein activity [Variation Ontology: 0053]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000491848GeneDxcriteria provided, single submitter
Uncertain significance
(Nov 18, 2016)
germlineclinical testing

Citation Link,

SCV000920680Gharavi Laboratory,Columbia Universitycriteria provided, single submitter
Uncertain significance
(Sep 16, 2018)
germlineresearch

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenonot providednot providednot providednot providednot providedresearch
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From GeneDx, SCV000491848.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

A variant of uncertain significance has been identified in the GLA gene. While the A309V variant has not been published in association with cardiomyopathy, it has been reported in a patient undergoing testing for Fabry disease (Lukas et al., 2016). However, functional studies show that cells expressing this variant have approximately 50% enzyme activity when compared to wild type cells which is consistent with a mild form of Fabry disease (Lukas et al., 2016). The A309V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved across species and where Valine is the wild type in one non-mammalian species. In silico analysis suggests this variant likely does not alter the protein structure/function. Nevertheless, the A309V was not observed in the Exome Aggregation Consortium.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.

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

From Gharavi Laboratory,Columbia University, SCV000920680.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 20, 2021

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