NM_000169.3(GLA):c.1192G>T (p.Glu398Ter) AND Fabry disease

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 23, 2016
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:: RCV000011493.8

Allele description [Variation Report for NM_000169.3(GLA):c.1192G>T (p.Glu398Ter)]

NM_000169.3(GLA):c.1192G>T (p.Glu398Ter)

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.1192G>T (p.Glu398Ter)

HGVS:

NC_000023.11:g.101397907C>A
NG_007119.1:g.15057G>T
NM_000169.3:c.1192G>TMANE SELECT
NM_001199973.2:c.300+2450C>A
NM_001199974.2:c.177+6085C>A
NM_001406747.1:c.1315G>T
NP_000160.1:p.Glu398Ter
NP_000160.1:p.Glu398Ter
NP_001393676.1:p.Glu439Ter
LRG_672t1:c.1192G>T
LRG_672:g.15057G>T
LRG_672p1:p.Glu398Ter
NC_000023.10:g.100652895C>A
NM_000169.2:c.1192G>T
NR_164783.1:n.1271G>T
NR_176252.1:n.1122G>T
NR_176253.1:n.1329G>T

Protein change:

E398*; GLU398TER

Links:

OMIM: 300644.0033; dbSNP: rs104894844

NCBI 1000 Genomes Browser:

rs104894844

Molecular consequence:

NM_001199973.2:c.300+2450C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001199974.2:c.177+6085C>A - intron variant - [Sequence Ontology: SO:0001627]
NR_164783.1:n.1271G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176252.1:n.1122G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176253.1:n.1329G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000169.3:c.1192G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406747.1:c.1315G>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000031725	OMIM	no assertion criteria provided	Pathogenic (Dec 1, 1993)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000695731	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (May 23, 2016)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 7504405, 8878432, 7911050 LabCorp Variant Classification Summary - May 2015.docx Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000031725

OMIM

no assertion criteria provided

Pathogenic
(Dec 1, 1993)

germline

literature only

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

SCV000695731

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(May 23, 2016)

germline

clinical testing

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

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Nature and frequency of mutations in the alpha-galactosidase A gene that cause Fabry disease.

Eng CM, Resnick-Silverman LA, Niehaus DJ, Astrin KH, Desnick RJ.

Am J Hum Genet. 1993 Dec;53(6):1186-97.

PubMed [citation]

PMID:: 7504405
PMCID:: PMC1682507

A carboxy-terminal truncation of human alpha-galactosidase A in a heterozygous female with Fabry disease and modification of the enzymatic activity by the carboxy-terminal domain. Increased, reduced, or absent enzyme activity depending on number of amino acid residues deleted.

Miyamura N, Araki E, Matsuda K, Yoshimura R, Furukawa N, Tsuruzoe K, Shirotani T, Kishikawa H, Yamaguchi K, Shichiri M.

J Clin Invest. 1996 Oct 15;98(8):1809-17.

PubMed [citation]

PMID:: 8878432
PMCID:: PMC507620

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000031725.1

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

Description

In a Hispanic patient with classic Fabry disease (301500), Eng et al. (1993) found a nonsense GAA-to-TAA mutation in exon 7 of the GLA gene, resulting in a glu398-to-ter (E398X) substitution.

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000695731.1

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

Description

Variant summary: The GLA c.1192G>T (p.Glu398X) variant results in a premature termination codon, predicted to cause a truncated (lacking 32 AA residues of the C terminus) or absent GLA protein due to nonsense mediated decay. One in silico tool predicts a damaging outcome for this variant. This variant is absent in 87740 control chromosomes. This variant has been reported to manifest a classical phenotype (Eng_AJHM_1993). Miyamura_JCI_1996 showed that deletions of 12 or more AA residues in the C-terminal region resulted in a complete loss of enzyme activity, indicating the functional importance of the C-terminal region. In addition, OMIM and HGMD classified this variant as pathogenic/DM (disease mutation). Taken together, this variant is 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: Sep 16, 2024

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