ClinVar Miner

Submissions for variant NM_005033.3(EXOSC9):c.538C>T (p.Arg180Cys)

gnomAD frequency: 0.00007  dbSNP: rs202225797
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre RCV005860250 SCV006552792 uncertain significance Pontocerebellar hypoplasia, type 1D 2025-09-10 criteria provided, single submitter clinical testing
Ambry Genetics RCV004980650 SCV005582463 uncertain significance Inborn genetic diseases 2024-11-20 criteria provided, single submitter clinical testing The c.538C>T (p.R180C) alteration is located in exon 6 (coding exon 6) of the EXOSC9 gene. This alteration results from a C to T substitution at nucleotide position 538, causing the arginine (R) at amino acid position 180 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001756966 SCV002133514 uncertain significance not provided 2021-09-05 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 180 of the EXOSC9 protein (p.Arg180Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs202225797, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with EXOSC9-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV001756966 SCV001995227 uncertain significance not provided 2021-02-05 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect

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