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NM_000169.3(GLA):c.3G>A (p.Met1Ile) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 21, 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:
RCV004629626.1

Allele description [Variation Report for NM_000169.3(GLA):c.3G>A (p.Met1Ile)]

NM_000169.3(GLA):c.3G>A (p.Met1Ile)

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.3G>A (p.Met1Ile)
HGVS:
  • NC_000023.11:g.101407901C>T
  • NG_007119.1:g.5063G>A
  • NG_016327.1:g.4699C>T
  • NM_000169.3:c.3G>AMANE SELECT
  • NM_001199973.2:c.301-4035C>T
  • NM_001199974.2:c.178-4035C>T
  • NM_001406747.1:c.3G>A
  • NM_001406748.1:c.3G>A
  • NM_001406749.1:c.3G>A
  • NP_000160.1:p.Met1Ile
  • NP_000160.1:p.Met1Ile
  • NP_001393676.1:p.Met1Ile
  • NP_001393677.1:p.Met1Ile
  • NP_001393678.1:p.Met1Ile
  • LRG_672t1:c.3G>A
  • LRG_672:g.5063G>A
  • LRG_672p1:p.Met1Ile
  • NC_000023.10:g.100662889C>T
  • NM_000169.2:c.3G>A
  • NR_164783.1:n.25G>A
  • NR_176252.1:n.25G>A
  • NR_176253.1:n.25G>A
Protein change:
M1I
Links:
dbSNP: rs2147487910
NCBI 1000 Genomes Browser:
rs2147487910
Molecular consequence:
  • NM_000169.3:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001406747.1:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001406748.1:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001406749.1:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001199973.2:c.301-4035C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001199974.2:c.178-4035C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000169.3:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406747.1:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406748.1:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406749.1:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_164783.1:n.25G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176252.1:n.25G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176253.1:n.25G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV005123517Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)
Pathogenic
(May 21, 2024)
germlineclinical testing

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

Citation Link

Summary from all submissions

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

Citations

PubMed

Frequency of de novo mutations in Japanese patients with Fabry disease.

Kobayashi M, Ohashi T, Iizuka S, Kaneshiro E, Higuchi T, Eto Y, Ida H.

Mol Genet Metab Rep. 2014;1:283-287.

PubMed [citation]
PMID:
27896102
PMCID:
PMC5121308

A sensitive mutation screening strategy for Fabry disease: detection of nine mutations in the alpha-galactosidase A gene.

Blanch LC, Meaney C, Morris CP.

Hum Mutat. 1996;8(1):38-43.

PubMed [citation]
PMID:
8807334

Details of each submission

From Ambry Genetics, SCV005123517.1

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

Description

The p.M1? pathogenic mutation (also known as c.3G>A) is located in coding exon 1 of the GLA gene and results from a G to A substitution at nucleotide position 3. This alters the methionine residue at the initiation codon (ATG). This alteration has been reported in individuals with Fabry disease, including a de novo occurrence in one individual (Blanch LC. Hum Mutat. 1996;8(1):38-43; Kobayashi M. Mol Genet Metab Rep. 2014 Aug 2;1:283-287). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, sequence variations that modify the initiation codon are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame. Based on the supporting evidence, this variant is interpreted as a disease-causing mutation.

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

Last Updated: Oct 26, 2024