NM_000169.3(GLA):c.116_119del (p.Thr39fs) AND Fabry disease

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 2, 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:: RCV002049433.5

Allele description [Variation Report for NM_000169.3(GLA):c.116_119del (p.Thr39fs)]

NM_000169.3(GLA):c.116_119del (p.Thr39fs)

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.116_119del (p.Thr39fs)

HGVS:

NC_000023.11:g.101407785_101407788del
NG_007119.1:g.5176_5179del
NG_016327.1:g.4583_4586del
NM_000169.3:c.116_119delMANE SELECT
NM_001199973.2:c.301-4151_301-4148del
NM_001199974.2:c.178-4151_178-4148del
NM_001406747.1:c.116_119del
NM_001406748.1:c.116_119del
NM_001406749.1:c.116_119del
NP_000160.1:p.Thr39Ilefs
NP_000160.1:p.Thr39fs
NP_001393676.1:p.Thr39fs
NP_001393677.1:p.Thr39fs
NP_001393678.1:p.Thr39fs
LRG_672t1:c.116_119del
LRG_672:g.5176_5179del
LRG_672p1:p.Thr39Ilefs
NC_000023.10:g.100662773_100662776del
NM_000169.2:c.116_119delCGCC
NR_164783.1:n.138_141del
NR_176252.1:n.138_141del
NR_176253.1:n.138_141del

Protein change:

T39fs

Links:

dbSNP: rs2147487313

NCBI 1000 Genomes Browser:

rs2147487313

Molecular consequence:

NM_000169.3:c.116_119del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406747.1:c.116_119del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406748.1:c.116_119del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406749.1:c.116_119del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001199973.2:c.301-4151_301-4148del - intron variant - [Sequence Ontology: SO:0001627]
NM_001199974.2:c.178-4151_178-4148del - intron variant - [Sequence Ontology: SO:0001627]
NR_164783.1:n.138_141del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176252.1:n.138_141del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176253.1:n.138_141del - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002117489	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 2, 2021)	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

SCV002117489

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 2, 2021)

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, SCV002117489.3

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

Description

This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with GLA-related conditions. This sequence change creates a premature translational stop signal (p.Thr39Ilefs*81) 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).

#	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

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