ClinVar Miner

Submissions for variant NM_000382.3(ALDH3A2):c.28C>T (p.Gln10Ter)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169182 SCV000220421 likely pathogenic Sjögren-Larsson syndrome 2014-06-17 criteria provided, single submitter literature only
Illumina Clinical Services Laboratory,Illumina RCV000169182 SCV000914756 uncertain significance Sjögren-Larsson syndrome 2018-03-07 criteria provided, single submitter clinical testing The ALDH3A2 c.28C>T (p.Gln10Ter) variant is a stop-gained variant that is predicted to result in premature termination of the protein and has been reported in a heterozygous state in a Spanish individual with Sjogren-Larsson syndrome (Rizzo et al. 1999). Cultured skin fibroblasts from this individual were shown to be deficient in FALDH, but the individual's full genotype was not clearly reported. In addition, Sanabria and Coco (2011) report the p.Gln10Ter variant in a heterozygous state in two siblings with Sjogren-Larsson syndrome who were also heterozygous for an in-frame deletion variant; the phase of the variants in these individuals was not reported. Control data are unavailable for the p.Gln10Ter variant, which is reported at a frequency of 0.000383 in the East Asian population of the Exome Aggregation Consortium. However, this frequency is based on only one allele in a region of poor sequence coverage. Based on the limited evidence available and the potential impact of stop-gained variants, the p.Gln10Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for Sjogren-Larsson syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV001041547 SCV001205171 pathogenic not provided 2019-12-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln10*) in the ALDH3A2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs72547554, ExAC 0.04%). This variant has been observed in individual(s) with Sjogren-Larsson syndrome (PMID: 21968182, 10577908). This variant is also known as Q10Ter in the literature. ClinVar contains an entry for this variant (Variation ID: 188833). Loss-of-function variants in ALDH3A2 are known to be pathogenic (PMID: 10577908, 10854114). For these reasons, this variant has been classified as Pathogenic.

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