ClinVar Miner

Submissions for variant NM_080632.3(UPF3B):c.1189A>G (p.Lys397Glu)

gnomAD frequency: 0.00001  dbSNP: rs898086981
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519345 SCV000617179 uncertain significance not provided 2015-10-13 criteria provided, single submitter clinical testing The K397E variant in the UPF3B gene has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The K397E variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The K397E variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Lysine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret K397E as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV002525112 SCV002977274 uncertain significance Syndromic X-linked intellectual disability 14 2022-03-18 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 449270). This variant has not been reported in the literature in individuals affected with UPF3B-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 397 of the UPF3B protein (p.Lys397Glu).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.