NM_000169.3(GLA):c.488del (p.Gly163fs) AND Fabry disease

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 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:: RCV003509440.3

Allele description [Variation Report for NM_000169.3(GLA):c.488del (p.Gly163fs)]

NM_000169.3(GLA):c.488del (p.Gly163fs)

Genes:

RPL36A-HNRNPH2:RPL36A-HNRNPH2 readthrough [Gene - HGNC]
GLA:galactosidase alpha [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

Xq22.1

Genomic location:

Preferred name:

NM_000169.3(GLA):c.488del (p.Gly163fs)

HGVS:

NC_000023.11:g.101401694del
NG_007119.1:g.11273del
NM_000169.3:c.488delMANE SELECT
NM_001199973.2:c.300+6237del
NM_001199974.2:c.177+9872del
NM_001406747.1:c.611del
NM_001406748.1:c.488del
NM_001406749.1:c.611del
NP_000160.1:p.Gly163Glufs
NP_000160.1:p.Gly163fs
NP_001393676.1:p.Gly204fs
NP_001393677.1:p.Gly163fs
NP_001393678.1:p.Gly204fs
LRG_672t1:c.485del
LRG_672:g.11273del
LRG_672p1:p.Gly163Glufs
NC_000023.10:g.100656679del
NC_000023.10:g.100656682del
NM_000169.2:c.485delG
NR_164783.1:n.510del
NR_176252.1:n.510del
NR_176253.1:n.510del

Protein change:

G163fs

Links:

dbSNP: rs2520895683

NCBI 1000 Genomes Browser:

rs2520895683

Molecular consequence:

NM_000169.3:c.488del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406747.1:c.611del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406748.1:c.488del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406749.1:c.611del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001199973.2:c.300+6237del - intron variant - [Sequence Ontology: SO:0001627]
NM_001199974.2:c.177+9872del - intron variant - [Sequence Ontology: SO:0001627]
NR_164783.1:n.510del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176252.1:n.510del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176253.1:n.510del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Fabry disease
Synonyms:: ALPHA-GALACTOSIDASE A DEFICIENCY; ANDERSON-FABRY DISEASE; CERAMIDE TRIHEXOSIDASE DEFICIENCY; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010526; MedGen: C0002986; Orphanet: 324; OMIM: 301500; Human Phenotype Ontology: HP:0001071

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004313513	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 11, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10666480, 12175777, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004313513

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 11, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Twenty novel mutations in the alpha-galactosidase A gene causing Fabry disease.

Topaloglu AK, Ashley GA, Tong B, Shabbeer J, Astrin KH, Eng CM, Desnick RJ.

Mol Med. 1999 Dec;5(12):806-11.

PubMed [citation]

PMID:: 10666480
PMCID:: PMC2230489

Fabry disease: 45 novel mutations in the alpha-galactosidase A gene causing the classical phenotype.

Shabbeer J, Yasuda M, Luca E, Desnick RJ.

Mol Genet Metab. 2002 May;76(1):23-30.

PubMed [citation]

PMID:: 12175777

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004313513.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Gly163Glufs*2) in the GLA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GLA are known to be pathogenic (PMID: 10666480, 12175777). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GLA-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as 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: May 16, 2025

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