ClinVar Miner

Submissions for variant NM_000155.4(GALT):c.961C>T (p.His321Tyr) (rs367543266)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000587990 SCV000695710 uncertain significance not provided 2017-03-21 criteria provided, single submitter clinical testing Variant summary: The GALT c.961C>T (p.His321Tyr) variant located in the Galactose-1-phosphate uridyl transferase, C-terminal domain (via InterPro) involves the alteration of a conserved nucleotide and 2/4 in silico tools (SNPs&GO not captured due to low reliability index) predict a benign outcome, although these predictions have yet to be functionally assessed. However, a publication, McCorvie_2016, predicts the variant to "remove interactions with zinc ion, steric clash with Leu37." This variant was found in 1/121402 control chromosomes at a frequency of 0.0000082, which does not exceed the estimated maximal expected allele frequency of a pathogenic GALT variant (0.0028868). The variant of interest has been reported in two affected individuals, one compound heterozygote (Webb_2003) indicating the variant to be a "leaky" mutation. Along with a clinical diagnostic laboratory classifying the variant as "pathogenic" and indicating a homozygous occurrence in an affected patient. Furthermore, multiple missense variants nearby, p.Ala320Thr, p.Pro325Leu, p.Arg328Cys, and p.Arg333Trp, have been classified by LCA as likely pathogenic/pathogenic, suggesting the area is a mutational hotspot important for protein function. Therefore, taking all available lines of evidence into consideration, the variant of interest has been classified as VUS - possibly pathogenic variant.
Counsyl RCV000022244 SCV000800644 uncertain significance Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2018-01-08 criteria provided, single submitter clinical testing
Research and Development, ARUP Laboratories RCV000022244 SCV000042928 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2012-12-04 no assertion criteria provided clinical testing Converted during submission to Pathogenic.

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