ClinVar Miner

Submissions for variant NM_025219.3(DNAJC5):c.448G>A (p.Val150Met) (rs146719477)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000499004 SCV000590092 uncertain significance not provided 2017-06-02 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the DNAJC5 gene. The V150M variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The V150M variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position that is conserved across species. However, the V150M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV001202163 SCV001373268 uncertain significance Neuronal ceroid lipofuscinosis 2019-09-10 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 150 of the DNAJC5 protein (p.Val150Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DNAJC5-related conditions. ClinVar contains an entry for this variant (Variation ID: 432374). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.

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