ClinVar Miner

Submissions for variant NM_003124.5(SPR):c.715C>T (p.Gln239Ter)

dbSNP: rs761407827
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003587022 SCV004274880 pathogenic Dystonic disorder 2024-08-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln239*) in the SPR gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 23 amino acid(s) of the SPR protein. This variant is present in population databases (rs761407827, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with SPR-related conditions. This variant disrupts a region of the SPR protein in which other variant(s) (p.Lys251*) have been determined to be pathogenic (PMID: 16917893, 18502672, 21431957, 21677200). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004701719 SCV005202571 pathogenic Dopa-responsive dystonia due to sepiapterin reductase deficiency 2024-07-12 criteria provided, single submitter clinical testing Variant summary: SPR c.715C>T (p.Gln239X) results in a premature termination codon, predicted to cause a truncation of the encoded protein. Although, nonsense mediated decay is not predicted, at least one pathogenic variant downstream has been observed in ClinVar. The variant allele was found at a frequency of 8e-06 in 251490 control chromosomes. To our knowledge, no occurrence of c.715C>T in individuals affected with Sepiapterin Reductase Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2720176). Based on the evidence outlined above, the variant was classified as pathogenic.

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