ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.955del (p.Tyr319fs) (rs786204454)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169089 SCV000220268 likely pathogenic Galactosylceramide beta-galactosidase deficiency 2014-04-24 criteria provided, single submitter literature only
GeneDx RCV000255073 SCV000321694 pathogenic not provided 2018-11-30 criteria provided, single submitter clinical testing The c.955delT variant in the GALC gene has been reported previously, using alternativenomenclature, in patients with Krabbe disease (Wenger et al., 1997; Lissens et al. 2007). The c.955delT variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. c.955delT causes a frameshift starting with codon Tyrosine 319, changes this amino acid to a Methionine residue and creates a premature Stop codon at position 6 of the new reading frame, denoted p.Tyr319MetfsX6. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. In summary, we interpret c.955delT to be a pathogenic variant.
Invitae RCV000169089 SCV001393346 pathogenic Galactosylceramide beta-galactosidase deficiency 2019-04-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr319Metfs*6) in the GALC gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with Krabbe disease (PMID: 9338580). This variant is also known as 906delT, c.907delT in the literature. ClinVar contains an entry for this variant (Variation ID: 188767). Loss-of-function variants in GALC are known to be pathogenic (PMID: 7437911, 9272171, 16607461). For these reasons, this variant has been classified as Pathogenic.

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