ClinVar Miner

Submissions for variant NM_199242.3(UNC13D):c.1152G>C (p.Gln384His)

gnomAD frequency: 0.00008  dbSNP: rs570422323
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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 RCV002004697 SCV002233424 uncertain significance Familial hemophagocytic lymphohistiocytosis 3 2021-09-17 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 384 of the UNC13D protein (p.Gln384His). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and histidine. This variant is present in population databases (rs570422323, ExAC 0.04%). This variant has not been reported in the literature in individuals affected with UNC13D-related conditions. 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: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available"). 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.
Neuberg Centre For Genomic Medicine, NCGM RCV002004697 SCV004048547 uncertain significance Familial hemophagocytic lymphohistiocytosis 3 criteria provided, single submitter clinical testing The missense variant in c.1152G>C (p.Gln384His) in UNC13D gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant has allele frequency of 0.008% in the gnomAD and novel in 1000 genome database. The amino acid Gln at position 384 is changed to a His changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by both SIFT and PolyPhen2. The residue is conserved across species. The amino acid change p.Gln384His in UNC13D is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. In the absence of another reportable variant/CNV the molecular diagnosis is not confirmed.

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