ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.433dup (p.Thr145fs) (rs1555383679)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668697 SCV000793341 likely pathogenic Galactosylceramide beta-galactosidase deficiency 2017-08-23 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000668697 SCV000919392 pathogenic Galactosylceramide beta-galactosidase deficiency 2018-04-27 criteria provided, single submitter clinical testing Variant summary: GALC c.433dupA (p.Thr145AsnfsX43) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.628A>T (p.Arg210X), c.1814dupA (p.Tyr605X)). The variant was absent in 245842 control chromosomes (gnomAD). The c.433dupA has been reported in the literature in an individual affected with Krabbe Disease (Puckett 2012). This publication also reported evidence evaluating an impact on protein function, demonstrating a severely decreased galactocerebrosidase activity measured in leukocytes (<10% of normal activity). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.

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