ClinVar Miner

Submissions for variant NM_001077350.3(NPRL3):c.1268C>T (p.Pro423Leu)

gnomAD frequency: 0.00031  dbSNP: rs200792895
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000653297 SCV000775176 uncertain significance Epilepsy, familial focal, with variable foci 3 2025-01-30 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 423 of the NPRL3 protein (p.Pro423Leu). This variant is present in population databases (rs200792895, gnomAD 0.04%), 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: 542796). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt NPRL3 protein function with a negative predictive value of 80%. 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.
CeGaT Center for Human Genetics Tuebingen RCV001090949 SCV001246742 likely benign not provided 2023-01-01 criteria provided, single submitter clinical testing NPRL3: BP4, BS2
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV001090949 SCV002011187 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV004025901 SCV004991690 likely benign Inborn genetic diseases 2024-03-04 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.

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