ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.205C>T (p.Arg69Ter)

gnomAD frequency: 0.00001  dbSNP: rs771111145
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins NTD LLC (GA) RCV000723390 SCV000227031 pathogenic not provided 2014-08-22 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000175531 SCV000695676 pathogenic Galactosylceramide beta-galactosidase deficiency 2017-01-19 criteria provided, single submitter clinical testing Variant summary: The GALC c.205C>T (p.Arg69X) variant results in a premature termination codon, predicted to cause a truncated or absent GALC protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant was found in 1/119986 control chromosomes at a frequency of 0.0000083, which does not exceed the estimated maximal expected allele frequency of a pathogenic GALC variant (0.0022361). The variant was reported in multiple affected individuals in the literature, and was shown to result in <10% GALC activity in a functional study where the variant was expressed in COS1 cells (Saavedra-Matiz_2016). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000175531 SCV000950536 pathogenic Galactosylceramide beta-galactosidase deficiency 2021-10-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg69*) 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 (rs771111145, ExAC 0.002%). This premature translational stop signal has been observed in individual(s) with Krabbe disease (PMID: 20886637). ClinVar contains an entry for this variant (Variation ID: 195020). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000175531 SCV001132200 likely pathogenic Galactosylceramide beta-galactosidase deficiency 2015-07-15 no assertion criteria provided clinical testing
PerkinElmer Genomics RCV000723390 SCV002021227 pathogenic not provided 2020-10-23 no assertion criteria provided clinical testing
Natera, Inc. RCV000175531 SCV002093659 pathogenic Galactosylceramide beta-galactosidase deficiency 2021-10-19 no assertion criteria provided clinical testing

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