ClinVar Miner

Submissions for variant NM_001077350.3(NPRL3):c.442C>T (p.Arg148Cys)

gnomAD frequency: 0.00029  dbSNP: rs201069648
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001036691 SCV001200068 uncertain significance Epilepsy, familial focal, with variable foci 3 2024-01-07 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 148 of the NPRL3 protein (p.Arg148Cys). This variant is present in population databases (rs201069648, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with NPRL3-related conditions. ClinVar contains an entry for this variant (Variation ID: 835740). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NPRL3 protein function. 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.
GeneDx RCV001664630 SCV001874763 likely benign not provided 2021-01-26 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001664630 SCV002585526 likely benign not provided 2022-08-01 criteria provided, single submitter clinical testing NPRL3: BP5
Ambry Genetics RCV003339433 SCV004059819 likely benign Inborn genetic diseases 2023-06-28 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Mayo Clinic Laboratories, Mayo Clinic RCV001664630 SCV004227485 uncertain significance not provided 2023-05-10 criteria provided, single submitter clinical testing BS2

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