Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000735161 | SCV000863362 | uncertain significance | not provided | 2018-09-13 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000802714 | SCV000942556 | uncertain significance | Nephronophthisis | 2024-10-23 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1104 of the NPHP3 protein (p.Tyr1104Cys). This variant is present in population databases (rs571618016, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with NPHP3-related conditions. ClinVar contains an entry for this variant (Variation ID: 598704). 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 expected to disrupt NPHP3 protein function with a positive 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. |
| Genome Diagnostics Laboratory, |
RCV002294376 | SCV002587488 | uncertain significance | Kidney disorder | 2021-06-24 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV002477735 | SCV002783618 | uncertain significance | Renal-hepatic-pancreatic dysplasia 1; Nephronophthisis 3; NPHP3-related Meckel-like syndrome | 2021-12-18 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV004594111 | SCV005086762 | uncertain significance | Nephronophthisis 3 | 2024-09-23 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3B. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Meckel syndrome 7 (MIM#267010), nephronophthisis 3 (MIM#604387) and renal-hepatic-pancreatic dysplasia 1 (MIM#208540). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from tyrosine to cysteine. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v2 and v3: 15 heterozygotes, 0 homozygotes). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated tetratricopeptide repeat domain (DECIPHER). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0809 - Previous evidence of pathogenicity for this variant is inconclusive. This variant has been reported as a VUS in ClinVar. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |