Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Division Of Personalized Genomic Medicine, |
RCV003330300 | SCV004037341 | uncertain significance | Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features | 2019-10-18 | criteria provided, single submitter | clinical testing | The c.1439G>A variant is a single base pair substitution at nucleotide c.1439 in the exon 5 of 14 of the ZSWIM gene, which creates a premature translational stop signal at amino acid 480 of 1216 (p.Trp480*). This variant has not been observed in the Genome Aggregation Database (gnomAD), indicating that it is not a common benign variant in the populations represented in this database. While it has not been reported in the literature or any human genetic disease databases, this nonsense variant is anticipated to result in nonsense mediated decay. However, recent literature evidence suggested that mRNA with a recurrent de novo nonsense variant, distal to this variant, may escape nonsense mediated decay and cellular consequences may be due to dominant negative effect caused by the presence of truncated ZSWIM6 protein (PMID: 29198722). |