ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.1709C>A (p.Thr570Asn)

gnomAD frequency: 0.00004  dbSNP: rs540808138
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV001815532 SCV002063147 uncertain significance not provided 2021-11-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002265977 SCV002547867 uncertain significance not specified 2022-05-13 criteria provided, single submitter clinical testing Variant summary: GALC c.1709C>A (p.Thr570Asn) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6e-05 in 248668 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in GALC causing Krabbe Disease (6e-05 vs 0.0022), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1709C>A in individuals affected with Krabbe Disease and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV001278154 SCV003447776 uncertain significance Galactosylceramide beta-galactosidase deficiency 2023-12-28 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 570 of the GALC protein (p.Thr570Asn). This variant is present in population databases (rs540808138, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with GALC-related conditions. ClinVar contains an entry for this variant (Variation ID: 990183). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Natera, Inc. RCV001278154 SCV001465150 uncertain significance Galactosylceramide beta-galactosidase deficiency 2020-07-20 no assertion criteria provided clinical testing

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