NM_000169.3(GLA):c.118C>G (p.Pro40Ala) AND Fabry disease

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 6, 2022
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:: RCV003050639.4

Allele description [Variation Report for NM_000169.3(GLA):c.118C>G (p.Pro40Ala)]

NM_000169.3(GLA):c.118C>G (p.Pro40Ala)

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.118C>G (p.Pro40Ala)

HGVS:

NC_000023.11:g.101407786G>C
NG_007119.1:g.5178C>G
NG_016327.1:g.4584G>C
NM_000169.3:c.118C>GMANE SELECT
NM_001199973.2:c.301-4150G>C
NM_001199974.2:c.178-4150G>C
NM_001406747.1:c.118C>G
NM_001406748.1:c.118C>G
NM_001406749.1:c.118C>G
NP_000160.1:p.Pro40Ala
NP_000160.1:p.Pro40Ala
NP_001393676.1:p.Pro40Ala
NP_001393677.1:p.Pro40Ala
NP_001393678.1:p.Pro40Ala
LRG_672t1:c.118C>G
LRG_672:g.5178C>G
LRG_672p1:p.Pro40Ala
NC_000023.10:g.100662774G>C
NM_000169.2:c.118C>G
NR_164783.1:n.140C>G
NR_176252.1:n.140C>G
NR_176253.1:n.140C>G

Protein change:

P40A

Molecular consequence:

NM_001199973.2:c.301-4150G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001199974.2:c.178-4150G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000169.3:c.118C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406747.1:c.118C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406748.1:c.118C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406749.1:c.118C>G - missense variant - [Sequence Ontology: SO:0001583]
NR_164783.1:n.140C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176252.1:n.140C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176253.1:n.140C>G - 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

Recent activity

Clear Turn Off Turn On

TMED9 [Ursus arctos]
TMED9 [Ursus arctos]
Gene ID:113261588

Gene

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
SCV003445380	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 6, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 19320660, 10916280, 12920095, 27356758, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003445380

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 6, 2022)

germline

clinical testing

PubMed (5)
[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

Echocardiography in Fabry disease: diagnostic value of endocardial border binary appearance.

Koskenvuo JW, Engblom E, Kantola IM, Hartiala JJ, Saraste A, Kiviniemi TO, Mononen I, Saraste M.

Clin Physiol Funct Imaging. 2009 May;29(3):177-80. doi: 10.1111/j.1475-097X.2008.00851.x.

PubMed [citation]

PMID:: 19320660

Fabry disease: twenty-two novel mutations in the alpha-galactosidase A gene and genotype/phenotype correlations in severely and mildly affected hemizygotes and heterozygotes.

Ashton-Prolla P, Tong B, Shabbeer J, Astrin KH, Eng CM, Desnick RJ.

J Investig Med. 2000 Jul;48(4):227-35.

PubMed [citation]

PMID:: 10916280

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003445380.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This missense change has been observed in individual(s) with Fabry disease (PMID: 19320660; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 40 of the GLA protein (p.Pro40Ala). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Pro40 amino acid residue in GLA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10916280, 12920095, 27356758). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine