ClinVar Miner

Submissions for variant NM_000154.2(GALK1):c.1144C>T (p.Gln382Ter)

gnomAD frequency: 0.00009  dbSNP: rs111033608
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000005985 SCV000797936 pathogenic Deficiency of galactokinase 2018-02-15 criteria provided, single submitter clinical testing
Invitae RCV000005985 SCV002242594 pathogenic Deficiency of galactokinase 2022-01-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln382*) in the GALK1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 11 amino acid(s) of the GALK1 protein. This variant is present in population databases (rs111033608, gnomAD 0.03%). This premature translational stop signal has been observed in individual(s) with galactokinase galactosemia (PMID: 10790206). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as Q832stop. ClinVar contains an entry for this variant (Variation ID: 5631). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects GALK1 function (PMID: 10790206). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000005985 SCV004020474 pathogenic Deficiency of galactokinase 2023-06-28 criteria provided, single submitter clinical testing Variant summary: GALK1 c.1144C>T (p.Gln382X) is located within the last exon of the gene and while it is not expected to undergo nonsense mediated decay, it results in a premature termination codon and is predicted to cause a truncation of the encoded protein, a known mechanism for disease. The variant allele was found at a frequency of 3.7e-05 in 245624 control chromosomes, almost exclusively in the Latino/Admixed American subpopulation in the gnomAD database. c.1144C>T has been reported in the literature as a biallelic genotype in multiple individuals from Costa Rica affected with Deficiency Of Galactokinase (e.g. Kolosha_2000). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function and found the variant results in approximately 10% of normal activity (Kolosha_2000). The following publication has been ascertained in the context of this evaluation (PMID: 10790206). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and both classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics RCV000005985 SCV004197935 pathogenic Deficiency of galactokinase 2023-08-09 criteria provided, single submitter clinical testing
OMIM RCV000005985 SCV000026167 pathogenic Deficiency of galactokinase 2000-01-01 no assertion criteria provided literature only

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