ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.379C>T (p.Arg127Ter)

gnomAD frequency: 0.00001  dbSNP: rs200532368
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493135 SCV000582687 pathogenic not provided 2019-07-08 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 25525159, 20886637, 23319190, 26795590, 27638593)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000590611 SCV000695677 pathogenic Galactosylceramide beta-galactosidase deficiency 2016-04-28 criteria provided, single submitter clinical testing Variant summary: The c.379C>T (p.Arg127*) variant in GALC gene is a nonsense mutation. The mutation is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. The variant has been reported in several affected individuals presented with infantile form of Krabbe via published reports. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.0032% exclusively in individuals of European descent (0.06%). This frequency does not exceed the maximal expected allele frequency for a pathogenic variant in GALC gene (0.22%). Taken together, the variant was classified as Pathogenic.
Invitae RCV000590611 SCV000827315 pathogenic Galactosylceramide beta-galactosidase deficiency 2024-01-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg127*) in the GALC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GALC are known to be pathogenic (PMID: 7437911, 9272171, 16607461). This variant is present in population databases (rs200532368, gnomAD 0.005%). This premature translational stop signal has been observed in individuals with autosomal recessive Krabbe disease (PMID: 20886637, 21824559, 27638593). This variant is also known as p.R111X. ClinVar contains an entry for this variant (Variation ID: 429982). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000590611 SCV001528218 pathogenic Galactosylceramide beta-galactosidase deficiency 2018-01-18 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported in patients with Krabbe disease [PMID 20886637]
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV000590611 SCV004013151 pathogenic Galactosylceramide beta-galactosidase deficiency 2023-04-27 criteria provided, single submitter clinical testing PVS1, PS3, PM2
Revvity Omics, Revvity RCV000493135 SCV004236388 pathogenic not provided 2023-04-03 criteria provided, single submitter clinical testing
Natera, Inc. RCV000590611 SCV002093653 pathogenic Galactosylceramide beta-galactosidase deficiency 2021-02-20 no assertion criteria provided clinical testing

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