ClinVar Miner

Submissions for variant NM_080911.3(UNG):c.593A>G (p.His198Arg)

gnomAD frequency: 0.00013  dbSNP: rs201388456
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000803713 SCV000943596 uncertain significance Hyper-IgM syndrome type 5 2022-08-19 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 198 of the UNG protein (p.His198Arg). This variant is present in population databases (rs201388456, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with UNG-related conditions. ClinVar contains an entry for this variant (Variation ID: 648895). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001192880 SCV001361305 uncertain significance not specified 2019-10-23 criteria provided, single submitter clinical testing Variant summary: UNG c.593A>G (p.His198Arg) results in a non-conservative amino acid change located in the Uracil-DNA glycosylase-like domain (IPR005122) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00016 in 251478 control chromosomes in the gnomAD database, including 1 homozygotes. This frequency is not significantly higher than expected for a pathogenic variant in UNG causing Hyper IgM Syndrome Type 5 (0.00016 vs 0.00016), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.593A>G in individuals affected with Hyper IgM Syndrome Type 5 and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics RCV001192880 SCV003703818 uncertain significance not specified 2022-01-18 criteria provided, single submitter clinical testing The c.593A>G (p.H198R) alteration is located in exon 5 (coding exon 5) of the UNG gene. This alteration results from a A to G substitution at nucleotide position 593, causing the histidine (H) at amino acid position 198 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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