ClinVar Miner

Submissions for variant NM_000169.3(GLA):c.639+5G>A

dbSNP: rs1928277140
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001217567 SCV001389413 uncertain significance Fabry disease 2019-10-29 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). 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. A different variant affecting this nucleotide (c.639+5G>T) has been determined to be pathogenic (PMID: 26691501). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic. Nucleotide substitutions within 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 may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in an individual affected with Fabry disease (PMID: 28723748). This sequence change falls in intron 4 of the GLA gene. It does not directly change the encoded amino acid sequence of the GLA protein, but it affects a nucleotide within the consensus splice site of the intron.

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