ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.195+1G>A (rs1009872980)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498766 SCV000589854 likely pathogenic not provided 2016-06-14 criteria provided, single submitter clinical testing The c.195+1 G>A splice site variant destroys the canonical splice donor site of intron 1. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Although this variant has no been previously reported to our knowledge, it is interpreted to be likely pathogenic.
Counsyl RCV000666305 SCV000790575 likely pathogenic Galactosylceramide beta-galactosidase deficiency 2017-03-29 criteria provided, single submitter clinical testing
Invitae RCV000666305 SCV001582066 pathogenic Galactosylceramide beta-galactosidase deficiency 2020-10-26 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 1 of the GALC gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in GALC are known to be pathogenic (PMID: 7437911, 9272171, 16607461). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has been observed in individual(s) with Krabbe disease (PMID: 28598007). This variant is also known as c.147+1G>A. ClinVar contains an entry for this variant (Variation ID: 432166). 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. For these reasons, this variant has been classified as Pathogenic.

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