NM_000169.3(GLA):c.610T>C (p.Trp204Arg) AND Fabry disease

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jan 8, 2020
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:: RCV000209164.6

Allele description [Variation Report for NM_000169.3(GLA):c.610T>C (p.Trp204Arg)]

NM_000169.3(GLA):c.610T>C (p.Trp204Arg)

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.610T>C (p.Trp204Arg)

HGVS:

NC_000023.11:g.101400695A>G
NG_007119.1:g.12269T>C
NM_000169.3:c.610T>CMANE SELECT
NM_001199973.2:c.300+5238A>G
NM_001199974.2:c.177+8873A>G
NM_001406747.1:c.733T>C
NM_001406748.1:c.610T>C
NP_000160.1:p.Trp204Arg
NP_000160.1:p.Trp204Arg
NP_001393676.1:p.Trp245Arg
NP_001393677.1:p.Trp204Arg
LRG_672t1:c.610T>C
LRG_672:g.12269T>C
LRG_672p1:p.Trp204Arg
NC_000023.10:g.100655683A>G
NM_000169.2:c.610T>C
NR_164783.1:n.632T>C
NR_176253.1:n.747T>C
P06280:p.Trp204Arg
p.(Trp204Arg)
p.W204R

Protein change:

W204R

Links:

UniProtKB: P06280#VAR_077391; dbSNP: rs869312148

NCBI 1000 Genomes Browser:

rs869312148

Molecular consequence:

NM_001199973.2:c.300+5238A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001199974.2:c.177+8873A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000169.3:c.610T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406747.1:c.733T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406748.1:c.610T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_164783.1:n.632T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176253.1:n.747T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Functional consequence:

Decreased function

Observations:

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000246055	Albrecht-Kossel-Institute, Medical University Rostock	no assertion criteria provided	Pathogenic (Jan 1, 2014)	inherited	research	PubMed (1) [See all records that cite this PMID]
SCV001250894	Biochemistry Metabolomics and Proteomics Laboratory, Necker Enfants Malades Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 8, 2020)	de novo	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000246055

Albrecht-Kossel-Institute, Medical University Rostock

no assertion criteria provided

Pathogenic
(Jan 1, 2014)

inherited

research

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

SCV001250894

Biochemistry Metabolomics and Proteomics Laboratory, Necker Enfants Malades Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jan 8, 2020)

de novo

clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	inherited	unknown	not provided	not provided	not provided	not provided	not provided	research
Caucasian	de novo	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Functional and Clinical Consequences of Novel α-Galactosidase A Mutations in Fabry Disease.

Lukas J, Scalia S, Eichler S, Pockrandt AM, Dehn N, Cozma C, Giese AK, Rolfs A.

Hum Mutat. 2016 Jan;37(1):43-51. doi: 10.1002/humu.22910. Epub 2015 Oct 27.

PubMed [citation]

PMID:: 26415523

Details of each submission

From Albrecht-Kossel-Institute, Medical University Rostock, SCV000246055.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	inherited	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Biochemistry Metabolomics and Proteomics Laboratory, Necker Enfants Malades Hospital, SCV001250894.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Caucasian	1	not provided	not provided	clinical testing	not provided

Description

Expression study of the c.610T>C variant showed an enzymatic activity around 0 and an absence of responsiveness to pharmacological chaperone (Lukas et al. Hum Mutat 2016, 37: 43). The variant reported 3 times in ClinVar was not found in population database such as GnomAD. Multiple lines of computational evidence support a deleterious effect on the gene or gene product : highly conserved nucleotide, highly conserved amino acid on 10 species up to domestic mosquito, variant considered as deleterious according to PolyPhen (probably damaging, score 1) and SIFT (predict not tolerated).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: May 16, 2025

ClinVar

Relating variation to medicine