Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003647130 | SCV004559658 | pathogenic | Pontocerebellar hypoplasia type 1B | 2023-09-26 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the EXOSC3 protein in which other variant(s) (p.Asp132Ala) have been determined to be pathogenic (PMID: 22544365, 23975261, 24524299, 25533962). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Disruption of the initiator codon has been observed in individual(s) with pontocerebellar hypoplasia (PMID: 23284067). This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the EXOSC3 mRNA. The next in-frame methionine is located at codon 174. |