Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003041427 | SCV003444508 | pathogenic | Coffin-Lowry syndrome; Intellectual disability, X-linked 19 | 2022-07-18 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exons 9 and 10 and introduces a premature termination codon (PMID: 11992250). The resulting mRNA is expected to undergo nonsense-mediated decay. This variant is also known as IVS10+5G>A. This variant has been observed in individuals with RPS6KA3-related conditions (PMID: 11992250; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 10 of the RPS6KA3 gene. It does not directly change the encoded amino acid sequence of the RPS6KA3 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. |