ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.1862G>A (p.Arg621His) (rs192911803)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001084937 SCV001005712 likely benign Galactosylceramide beta-galactosidase deficiency 2020-12-01 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000675253 SCV000800901 likely benign not provided 2017-05-15 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000675253 SCV001551873 likely benign not provided no assertion criteria provided clinical testing The GALC p.Arg595His variant was not identified in the literature nor was it identified in Cosmic and LOVD 3.0. The variant was identified in dbSNP (ID: rs192911803), ClinVar (classified as likely benign by Mayo Clinic), and in control databases in 211 of 280146 chromosomes (2 homozygous) at a frequency of 0.000753 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 188 of 24156 chromosomes (freq: 0.007783), Latino in 13 of 35328 chromosomes (freq: 0.000368), South Asian in 6 of 30584 chromosomes (freq: 0.000196), Other in 1 of 7128 chromosomes (freq: 0.00014) and European (non-Finnish) in 3 of 128108 chromosomes (freq: 0.000023), but was not observed in the Ashkenazi Jewish, East Asian, and European (Finnish) populations. The p.Arg595 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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