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NM_000169.3(GLA):c.999+1G>T AND Fabry disease

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 1, 1992
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000011467.7

Allele description [Variation Report for NM_000169.3(GLA):c.999+1G>T]

NM_000169.3(GLA):c.999+1G>T

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.999+1G>T
HGVS:
  • NC_000023.11:g.101398369C>A
  • NG_007119.1:g.14595G>T
  • NM_000169.3:c.999+1G>TMANE SELECT
  • NM_001199973.2:c.300+2912C>A
  • NM_001199974.2:c.177+6547C>A
  • NM_001406747.1:c.1122+1G>T
  • NM_001406748.1:c.1000G>T
  • NP_001393677.1:p.Val334Leu
  • LRG_672t1:c.999+1G>T
  • LRG_672:g.14595G>T
  • NC_000023.10:g.100653357C>A
  • NM_000169.2:c.999+1G>T
Note:
ClinGen staff contributed the HGVS expression for this variant.
Nucleotide change:
IVS6DS, G-T, +1
Protein change:
V334L
Links:
OMIM: 300644.0007; dbSNP: rs1603038103
NCBI 1000 Genomes Browser:
rs1603038103
Molecular consequence:
  • NM_001199973.2:c.300+2912C>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001199974.2:c.177+6547C>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406748.1:c.1000G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000169.3:c.999+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406747.1:c.1122+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000031699OMIM
no assertion criteria provided
Pathogenic
(Apr 1, 1992) 		germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Invariant exon skipping in the human alpha-galactosidase A pre-mRNA: Ag+1 to t substitution in a 5'-splice site causing Fabry disease.

Sakuraba H, Eng CM, Desnick RJ, Bishop DF.

Genomics. 1992 Apr;12(4):643-50.

PubMed [citation]
PMID:
1315304

The human growth hormone locus: nucleotide sequence, biology, and evolution.

Chen EY, Liao YC, Smith DH, Barrera-Saldaña HA, Gelinas RE, Seeburg PH.

Genomics. 1989 May;4(4):479-97.

PubMed [citation]
PMID:
2744760

Details of each submission

From OMIM, SCV000031699.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In 3 affected brothers from a Japanese family with Fabry disease (301500), Sakuraba et al. (1992) identified deletion of exon 6 due to a G-to-T transversion at the first nucleotide of the 5-prime splice site of intron 6 of the GLA gene. Sakuraba et al. (1992) stated that this was the first G-to-T transversion of a mammalian 5-prime splice site that consistently eliminated the preceding exon. Sakuraba et al. (1992) gave a tabulation of various mammalian 5-prime consensus splice site mutations that lead to exon skipping and in most cases use of cryptic splice sites. They pointed out that glycophorin B (GYPB; 617923) of the Ss blood group (111740) differs from glycophorin A (GYPA; 617922) of the MN blood group (111300) by 2 changes at the 5-prime splice site of intron 3 which presumably took place after duplication of the progenitor gene. As indicated in their Table 1, the gene for growth hormone-like (GH2; 139240) differs from that for growth hormone (GH1; 139250) by a G-to-A transition at position +1 of intron 2 in the duplicated gene (Chen et al., 1989).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 16, 2024