Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Broad Center for Mendelian Genomics, |
RCV002810027 | SCV003761258 | uncertain significance | Spinocerebellar ataxia type 21 | 2023-01-25 | criteria provided, single submitter | curation | The homozygous p.Ser16Ter variant in TMEM240 was identified by our study in two siblings with spinocerebellar ataxia (PMID: 34791078). These two affected individuals were homozygotes, which increases the likelihood that the p.Ser16Ter variant is pathogenic (PMID: 34791078). This variant was absent from large population studies. This nonsense variant leads to a premature termination codon at position 16, which is predicted to lead to a truncated or absent protein. While there is some evidence to suggest that loss of function of the TMEM240 gene is a disease mechanism in spinocerebellar ataxia 21, this association is not yet strongly established based on the criteria laid out in Tayoun, 2018 (PMID: 30192042). In summary, the clinical significance of the p.Ser16Ter variant is uncertain. ACMG/AMP Criteria applied: PVS1_Supporting, PM2_Supporting, PM3_Supporting (Richards 2015). |