ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.328+1G>T

gnomAD frequency: 0.00001  dbSNP: rs779701490
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000409516 SCV000486247 likely pathogenic Galactosylceramide beta-galactosidase deficiency 2016-04-21 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000409516 SCV001388413 pathogenic Galactosylceramide beta-galactosidase deficiency 2025-01-21 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 3 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). This variant is present in population databases (rs779701490, gnomAD 0.006%). Disruption of this splice site has been observed in individual(s) with Krabbe disease (internal data). ClinVar contains an entry for this variant (Variation ID: 370833). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000409516 SCV005637592 likely pathogenic Galactosylceramide beta-galactosidase deficiency 2024-05-14 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV000409516 SCV005849160 likely pathogenic Galactosylceramide beta-galactosidase deficiency 2023-06-22 criteria provided, single submitter clinical testing The observed splice donor variant c.328+1G>T in GALC gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with 0.001% allele frequency in gnomAD Exomes. It has been submitted to ClinVar as Likely Pathogenic/ Pathogenic. This variant is predicted to be Likely damaging by SpliceAI Prediction. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing (Xu C, et al., 2006). For these reasons, this variant has been classified as Likely Pathogenic.

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