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NM_000169.3(GLA):c.164_171delinsTCTGCCTA (p.Asp55_Gln57delinsValCysLeu) AND Fabry disease

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 11, 2023
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:
RCV003387920.1

Allele description [Variation Report for NM_000169.3(GLA):c.164_171delinsTCTGCCTA (p.Asp55_Gln57delinsValCysLeu)]

NM_000169.3(GLA):c.164_171delinsTCTGCCTA (p.Asp55_Gln57delinsValCysLeu)

Genes:
RPL36A-HNRNPH2:RPL36A-HNRNPH2 readthrough [Gene - HGNC]
GLA:galactosidase alpha [Gene - OMIM - HGNC]
Variant type:
Indel
Cytogenetic location:
Xq22.1
Genomic location:
Preferred name:
NM_000169.3(GLA):c.164_171delinsTCTGCCTA (p.Asp55_Gln57delinsValCysLeu)
HGVS:
  • NC_000023.11:g.101407733_101407740delinsTAGGCAGA
  • NG_007119.1:g.5224_5231delinsTCTGCCTA
  • NG_016327.1:g.4531_4538delinsTAGGCAGA
  • NM_000169.3:c.164_171delinsTCTGCCTAMANE SELECT
  • NM_001199973.2:c.301-4203_301-4196delinsTAGGCAGA
  • NM_001199974.2:c.178-4203_178-4196delinsTAGGCAGA
  • NM_001406747.1:c.164_171delinsTCTGCCTA
  • NM_001406748.1:c.164_171delinsTCTGCCTA
  • NM_001406749.1:c.164_171delinsTCTGCCTA
  • NP_000160.1:p.Asp55_Gln57delinsValCysLeu
  • NP_000160.1:p.Asp55_Gln57delinsValCysLeu
  • NP_001393676.1:p.Asp55_Gln57delinsValCysLeu
  • NP_001393677.1:p.Asp55_Gln57delinsValCysLeu
  • NP_001393678.1:p.Asp55_Gln57delinsValCysLeu
  • LRG_672t1:c.164_171delinsTCTGCCTA
  • LRG_672:g.5224_5231delinsTCTGCCTA
  • NC_000023.10:g.100662721_100662728delinsTAGGCAGA
  • NM_000169.2:c.164_171delACTGCCAGinsTCTGCCTA
  • NM_000169.2:c.164_171delinsTCTGCCTA
  • NR_164783.1:n.186_193delinsTCTGCCTA
  • NR_176252.1:n.186_193delinsTCTGCCTA
  • NR_176253.1:n.186_193delinsTCTGCCTA
Links:
dbSNP: rs1569306036
NCBI 1000 Genomes Browser:
rs1569306036
Molecular consequence:
  • NM_001199973.2:c.301-4203_301-4196delinsTAGGCAGA - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001199974.2:c.178-4203_178-4196delinsTAGGCAGA - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000169.3:c.164_171delinsTCTGCCTA - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406747.1:c.164_171delinsTCTGCCTA - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406748.1:c.164_171delinsTCTGCCTA - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406749.1:c.164_171delinsTCTGCCTA - missense variant - [Sequence Ontology: SO:0001583]
  • NR_164783.1:n.186_193delinsTCTGCCTA - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176252.1:n.186_193delinsTCTGCCTA - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176253.1:n.186_193delinsTCTGCCTA - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Fabry disease
Synonyms:
Angiokeratoma, diffuse; Anderson-Fabry disease; Hereditary dystopic lipidosis; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010526; MedGen: C0002986; Orphanet: 324; OMIM: 301500; Human Phenotype Ontology: HP:0001071

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV004099690Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Pathogenic
(Sep 11, 2023)
germlineclinical testing

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

Citation Link

Summary from all submissions

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

Citations

PubMed

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004099690.1

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

Description

Variant summary: GLA c.164_171delinsTCTGCCTA (p.Asp55_Gln57delinsValCysLeu) results in an in-frame deletion-insertion that is predicted to delete/insert 3 amino acids from the protein and also cause changes in 2 amino acids. The variant was absent in 183298 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. A variant resulting in the equivalent amino acid changes (annotated as the double variant D55V/Q57L) has been reported in patients affected with Fabry disease (Benjamin_2009). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function of cells derived from patients with the aforementioned amino acid changes, finding a severe loss of alpha-Gal A activity (Benjamin_2009). The following publication has been ascertained in the context of this evaluation (PMID: 19387866). One submitter has cited a clinical-significance assessment for this variant to ClinVar after 2014 and has classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Sep 16, 2024