ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.1004A>G (p.Tyr335Cys)

gnomAD frequency: 0.00001  dbSNP: rs757407613
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000806470 SCV000946473 pathogenic Galactosylceramide beta-galactosidase deficiency 2023-07-06 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects GALC function (PMID: 10234611, 27126738, 27638593). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GALC protein function. ClinVar contains an entry for this variant (Variation ID: 651170). This missense change has been observed in individual(s) with infantile Krabbe disease (PMID: 10234611, 22115770). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs757407613, gnomAD 0.003%). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 335 of the GALC protein (p.Tyr335Cys).
GeneDx RCV002279541 SCV002567620 pathogenic not provided 2022-02-15 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect (significantly reduced GALC activity) (Fu et al., 1999); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 10234611, 27638593, 27126738, 22115770)
Natera, Inc. RCV000806470 SCV002093639 pathogenic Galactosylceramide beta-galactosidase deficiency 2020-08-27 no assertion criteria provided clinical testing

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