ClinVar Miner

Submissions for variant NM_000155.4(GALT):c.687+9G>C (rs117998880)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000871944 SCV000479764 uncertain significance Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Integrated Genetics/Laboratory Corporation of America RCV000588651 SCV000695699 likely benign not specified 2018-02-02 criteria provided, single submitter clinical testing Variant summary: GALT c.687+9G>C alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing. 4/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 198/277122 control chromosomes at a frequency of 0.0007145. Although, this frequency is not significantly higher than expected for a pathogenic variant in GALT causing Galactosemia (0.00071 vs 0.0029), the presence of a homozygous individual in gnomAD suggests the benign nature of the variant. To our knowledge, no occurrence of c.687+9G>C in individuals affected with Galactosemia and no experimental evidence demonstrating its impact on protein function have been reported in the literature. Co-occurrences with other pathogenic variant(s), (GALT c.-119_-116delGTCA; GALT c.[-1039_753del3162; 820+51_*789del2294ins12]) have been reported in unaffected individuals undergoing carrier screening testing in internal specimens, providing supporting evidence for a benign role. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as Likely Benign.
Invitae RCV000871944 SCV001013686 likely benign Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2019-12-31 criteria provided, single submitter clinical testing

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