Submissions for variant NM_017999.5(RNF31):c.515A>G (p.Gln172Arg)

gnomAD frequency: 0.00003  dbSNP: rs781741612

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV002208772	SCV002495934	uncertain significance	not provided	2021-03-15	criteria provided, single submitter	clinical testing	RNF31 NM_017999.4 exon 4 p.Gln172Arg (c.515A>G): This variant has not been reported in the literature but is present in 0.01% (5/34526) of Latino alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/14-24617870-A-G?dataset=gnomad_r2_1). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002208772	SCV003473341	uncertain significance	not provided	2024-11-11	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 172 of the RNF31 protein (p.Gln172Arg). This variant is present in population databases (rs781741612, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with RNF31-related conditions. ClinVar contains an entry for this variant (Variation ID: 1675122). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.