NM_000169.3(GLA):c.484T>C (p.Trp162Arg) AND Angiokeratoma corporis diffusum

Clinical significance:Likely pathogenic (Last evaluated: Jul 2, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_000169.3(GLA):c.484T>C (p.Trp162Arg)]

NM_000169.3(GLA):c.484T>C (p.Trp162Arg)

RPL36A-HNRNPH2:RPL36A-HNRNPH2 readthrough [Gene - HGNC]
GLA:galactosidase alpha [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000169.3(GLA):c.484T>C (p.Trp162Arg)
  • NC_000023.11:g.101401695A>G
  • NG_007119.1:g.11269T>C
  • NM_000169.2:c.484T>C
  • NM_000169.3:c.484T>CMANE SELECT
  • NM_001199973.2:c.300+6238A>G
  • NM_001199974.2:c.177+9873A>G
  • NP_000160.1:p.Trp162Arg
  • NP_000160.1:p.Trp162Arg
  • LRG_672t1:c.484T>C
  • LRG_672:g.11269T>C
  • LRG_672p1:p.Trp162Arg
  • NC_000023.10:g.100656683A>G
  • NR_164783.1:n.506T>C
  • P06280:p.Trp162Arg
Protein change:
W162R; TRP162ARG
UniProtKB: P06280#VAR_000458; OMIM: 300644.0016; dbSNP: rs28935196
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001199973.2:c.300+6238A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001199974.2:c.177+9873A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000169.2:c.484T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000169.3:c.484T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_164783.1:n.506T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]


Angiokeratoma corporis diffusum
Fabry disease; Angiokeratoma, diffuse; Anderson-Fabry disease; See all synonyms [MedGen]
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)
SCV000031707OMIMno assertion criteria providedPathogenic
(Dec 1, 1993)
germlineliterature only

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

SCV000828383Invitaecriteria provided, single submitter
Likely pathogenic
(Jul 2, 2018)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only



Results of a nationwide screening for Anderson-Fabry disease among dialysis patients.

Kotanko P, Kramar R, Devrnja D, Paschke E, Voigtländer T, Auinger M, Pagliardini S, Spada M, Demmelbauer K, Lorenz M, Hauser AC, Kofler HJ, Lhotta K, Neyer U, Pronai W, Wallner M, Wieser C, Wiesholzer M, Zodl H, Födinger M, Sunder-Plassmann G.

J Am Soc Nephrol. 2004 May;15(5):1323-9. Erratum in: J Am Soc Nephrol. 2004 Aug;15(8):1a. J Am Soc Nephrol. 2004 Sep;15(9):A4.

PubMed [citation]

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]
See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000031707.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)


In an Italian patient with classic Fabry disease (301500), Eng et al. (1993) found a T-to-C transition in exon 3 of the GLA gene, resulting in a trp162-to-arg (W162R) substitution.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV000828383.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)


This sequence change replaces tryptophan with arginine at codon 162 of the GLA protein (p.Trp162Arg). The tryptophan residue is highly conserved and there is a moderate physicochemical difference between tryptophan and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported as hemizygous in individuals affected with Fabry disease (PMID: 15100373, 12778775, 7504405). ClinVar contains an entry for this variant (Variation ID: 10728). Experimental studies have shown that this missense change results in a GLA protein with no alpha-galactosidase A enzyme activity (PMID: 21598360). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Nov 20, 2021

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