ClinVar Miner

Submissions for variant NM_016042.4(EXOSC3):c.712T>C (p.Trp238Arg)

dbSNP: rs672601332
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000024370 SCV004294309 likely pathogenic Pontocerebellar hypoplasia type 1B 2023-05-13 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects EXOSC3 function (PMID: 22544365, 27777260, 28053271). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt EXOSC3 protein function. ClinVar contains an entry for this variant (Variation ID: 31692). This missense change has been observed in individual(s) with pontocerebellar hypoplasia (PMID: 22544365). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. 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 replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 238 of the EXOSC3 protein (p.Trp238Arg).
OMIM RCV000024370 SCV000045663 pathogenic Pontocerebellar hypoplasia type 1B 2012-04-29 no assertion criteria provided literature only

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