ClinVar Miner

Submissions for variant NM_000169.3(GLA):c.369+3G>A

dbSNP: rs1333591942
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000622002 SCV000739883 uncertain significance Cardiovascular phenotype 2013-08-07 criteria provided, single submitter clinical testing ​The c.369+3G>A intronic variant results from a G to A substitution three nucleotides after coding exon 2 in the GLA gene. This variant was not reported in population-based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project. Based on nucleotide sequence alignment, this position is well conserved in available vertebrate species, though adenosine is the reference nucleotide in three species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to strengthen the native donor splice site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001860410 SCV002253775 uncertain significance Fabry disease 2023-11-09 criteria provided, single submitter clinical testing This sequence change falls in intron 2 of the GLA gene. It does not directly change the encoded amino acid sequence of the GLA protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GLA-related conditions. ClinVar contains an entry for this variant (Variation ID: 520251). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.
All of Us Research Program, National Institutes of Health RCV001860410 SCV004830502 uncertain significance Fabry disease 2023-09-04 criteria provided, single submitter clinical testing This variant causes a G to A nucleotide substitution at the +3 position of intron 2 of the GLA gene. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with GLA-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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