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NM_000169.3(GLA):c.170A>C (p.Gln57Pro) AND Fabry disease

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Aug 5, 2021
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:
RCV001563580.3

Allele description [Variation Report for NM_000169.3(GLA):c.170A>C (p.Gln57Pro)]

NM_000169.3(GLA):c.170A>C (p.Gln57Pro)

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.170A>C (p.Gln57Pro)
HGVS:
  • NC_000023.11:g.101407734T>G
  • NG_007119.1:g.5230A>C
  • NG_016327.1:g.4532T>G
  • NM_000169.3:c.170A>CMANE SELECT
  • NM_001199973.2:c.301-4202T>G
  • NM_001199974.2:c.178-4202T>G
  • NM_001406747.1:c.170A>C
  • NM_001406748.1:c.170A>C
  • NM_001406749.1:c.170A>C
  • NP_000160.1:p.Gln57Pro
  • NP_000160.1:p.Gln57Pro
  • NP_001393676.1:p.Gln57Pro
  • NP_001393677.1:p.Gln57Pro
  • NP_001393678.1:p.Gln57Pro
  • LRG_672t1:c.170A>C
  • LRG_672:g.5230A>C
  • LRG_672p1:p.Gln57Pro
  • NC_000023.10:g.100662722T>G
  • NM_000169.2:c.170A>C
  • NR_164783.1:n.192A>C
  • NR_176252.1:n.192A>C
  • NR_176253.1:n.192A>C
Protein change:
Q57P
Links:
dbSNP: rs869312260
NCBI 1000 Genomes Browser:
rs869312260
Molecular consequence:
  • NM_001199973.2:c.301-4202T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001199974.2:c.178-4202T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000169.3:c.170A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406747.1:c.170A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406748.1:c.170A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406749.1:c.170A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_164783.1:n.192A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176252.1:n.192A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176253.1:n.192A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
1

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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV0017865523billion
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Aug 5, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot provided1not 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

A pharmacogenetic approach to identify mutant forms of α-galactosidase A that respond to a pharmacological chaperone for Fabry disease.

Wu X, Katz E, Della Valle MC, Mascioli K, Flanagan JJ, Castelli JP, Schiffmann R, Boudes P, Lockhart DJ, Valenzano KJ, Benjamin ER.

Hum Mutat. 2011 Aug;32(8):965-77. doi: 10.1002/humu.21530. Epub 2011 Jul 12.

PubMed [citation]
PMID:
21598360
PMCID:
PMC3170878
See all PubMed Citations (4)

Details of each submission

From 3billion, SCV001786552.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (4)

Description

The heterozygous variant (NM_000169.2:c.170A>C) is absent from gnomAD v2.1.1. It is located in an exonic hotspot where pathogenic variants are frequently reported. Different pathogenic amino acid change [c.164A>T/c.171G>A (p.Asp55Val/Gln57Leu)] has been reported at the same codon (PMID 19387866 and 21598360). Missense variant of GLA gene is a common mechanism associated with Fabry disease. Patient's phenotype including stroke and proteinuria is considered as compatible with Fabry disease. Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot provided1not providednot providednot provided

Last Updated: Sep 16, 2024