Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001365282 | SCV001561547 | uncertain significance | Nephronophthisis | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 235 of the NPHP3 protein (p.Gly235Arg). This variant is present in population databases (rs368570508, gnomAD 0.02%). This missense change has been observed in individual(s) with nephronophthisis (PMID: 30586318). ClinVar contains an entry for this variant (Variation ID: 562444). 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) performed at Invitae indicates that this missense variant is not expected to disrupt NPHP3 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. |
| Fulgent Genetics, |
RCV002485581 | SCV002793446 | uncertain significance | Renal-hepatic-pancreatic dysplasia 1; Nephronophthisis 3; NPHP3-related Meckel-like syndrome | 2021-10-29 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002531426 | SCV003718993 | uncertain significance | Inborn genetic diseases | 2021-11-09 | criteria provided, single submitter | clinical testing | The c.703G>A (p.G235R) alteration is located in exon 4 (coding exon 4) of the NPHP3 gene. This alteration results from a G to A substitution at nucleotide position 703, causing the glycine (G) at amino acid position 235 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Gharavi Laboratory, |
RCV000681924 | SCV000809407 | likely pathogenic | not provided | 2018-09-16 | no assertion criteria provided | research | |
| Prevention |
RCV004740407 | SCV005350800 | uncertain significance | NPHP3-related disorder | 2024-03-21 | no assertion criteria provided | clinical testing | The NPHP3 c.703G>A variant is predicted to result in the amino acid substitution p.Gly235Arg. This variant in the homozygous condition was reported in an individual with Nephronophthisis 3, who also carried a hemizygous variant in COL4A5 (Table S7, Groopman et al. 2019. PubMed ID: 30586318). This variant is reported in 0.016% of alleles in individuals of African descent in gnomAD. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |