NM_000169.3(GLA):c.812G>T (p.Gly271Val) AND Cardiovascular phenotype

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Apr 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:: RCV002423245.4

Allele description [Variation Report for NM_000169.3(GLA):c.812G>T (p.Gly271Val)]

NM_000169.3(GLA):c.812G>T (p.Gly271Val)

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.812G>T (p.Gly271Val)

HGVS:

NC_000023.11:g.101398557C>A
NG_007119.1:g.14407G>T
NM_000169.3:c.812G>TMANE SELECT
NM_001199973.2:c.300+3100C>A
NM_001199974.2:c.177+6735C>A
NM_001406747.1:c.935G>T
NM_001406748.1:c.812G>T
NP_000160.1:p.Gly271Val
NP_000160.1:p.Gly271Val
NP_001393676.1:p.Gly312Val
NP_001393677.1:p.Gly271Val
LRG_672t1:c.812G>T
LRG_672:g.14407G>T
LRG_672p1:p.Gly271Val
NC_000023.10:g.100653545C>A
NM_000169.2:c.812G>T
NR_164783.1:n.891G>T
NR_176252.1:n.742G>T
NR_176253.1:n.949G>T

Protein change:

G271V

Links:

dbSNP: rs869312429

NCBI 1000 Genomes Browser:

rs869312429

Molecular consequence:

NM_001199973.2:c.300+3100C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001199974.2:c.177+6735C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000169.3:c.812G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406747.1:c.935G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406748.1:c.812G>T - missense variant - [Sequence Ontology: SO:0001583]
NR_164783.1:n.891G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176252.1:n.742G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176253.1:n.949G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002679493	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Apr 4, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16595074, 19387866, 20498269, 21598360 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002679493

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Apr 4, 2024)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Fabry disease: identification of 50 novel alpha-galactosidase A mutations causing the classic phenotype and three-dimensional structural analysis of 29 missense mutations.

Shabbeer J, Yasuda M, Benson SD, Desnick RJ.

Hum Genomics. 2006 Mar;2(5):297-309.

PubMed [citation]

PMID:: 16595074
PMCID:: PMC3500179

The pharmacological chaperone 1-deoxygalactonojirimycin increases alpha-galactosidase A levels in Fabry patient cell lines.

Benjamin ER, Flanagan JJ, Schilling A, Chang HH, Agarwal L, Katz E, Wu X, Pine C, Wustman B, Desnick RJ, Lockhart DJ, Valenzano KJ.

J Inherit Metab Dis. 2009 Jun;32(3):424-40. doi: 10.1007/s10545-009-1077-0. Epub 2009 Apr 18.

PubMed [citation]

PMID:: 19387866

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV002679493.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The p.G271V variant (also known as c.812G>T), located in coding exon 6 of the GLA gene, results from a G to T substitution at nucleotide position 812. The glycine at codon 271 is replaced by valine, an amino acid with dissimilar properties. This variant was identified in an individual with classic Fabry disease (Shabbeer J et al. Hum. Genomics, 2006 Mar;2:297-309). Alpha galactosidase activity in patient lymphoblasts and HEK293 cells was absent (Benjamin ER et al. J. Inherit. Metab. Dis., 2009 Jun;32:424-40; Wu X et al. Hum. Mutat., 2011 Aug;32:965-77). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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