ClinVar Miner

Submissions for variant NM_001083116.3(PRF1):c.161G>A (p.Arg54His)

gnomAD frequency: 0.00025  dbSNP: rs150357196
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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 RCV001216687 SCV001388496 uncertain significance Familial hemophagocytic lymphohistiocytosis 2 2022-08-19 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 54 of the PRF1 protein (p.Arg54His). This variant is present in population databases (rs150357196, gnomAD 0.09%). This variant has not been reported in the literature in individuals affected with PRF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 945931). 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"). This variant disrupts the p.Arg54 amino acid residue in PRF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 14757862, 17266056, 21152410, 22437823). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
PreventionGenetics, part of Exact Sciences RCV003414010 SCV004116983 uncertain significance PRF1-related disorder 2023-08-21 criteria provided, single submitter clinical testing The PRF1 c.161G>A variant is predicted to result in the amino acid substitution p.Arg54His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.093% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/10-72360498-C-T). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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