Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Broad Center for Mendelian Genomics, |
RCV000785914 | SCV000924490 | pathogenic | Nephronophthisis 3 | 2018-06-15 | criteria provided, single submitter | research | The heterozygous p.Arg392Ter variant was identified by our study in the compound heterozygous state, with a pathogenic variant, in one individual with nephronophthisis. This variant has been identified in <0.01% (1/25790) of European (Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs143197357). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Loss of function of the NPHP3 gene is an established disease mechanism in autosomal recessive nephronophthisis, and this is a loss of function variant. In summary, this variant is pathogenic. |
Fulgent Genetics, |
RCV002507353 | SCV002816560 | pathogenic | Renal-hepatic-pancreatic dysplasia 1; Nephronophthisis 3; NPHP3-related Meckel-like syndrome | 2022-01-08 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV003133591 | SCV003817438 | likely pathogenic | not provided | 2021-12-28 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003748283 | SCV004535219 | pathogenic | Nephronophthisis | 2024-01-21 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg392*) in the NPHP3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NPHP3 are known to be pathogenic (PMID: 18371931, 23559409). This variant is present in population databases (no rsID available, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with juvenile nephronophthisis (PMID: 31131822). ClinVar contains an entry for this variant (Variation ID: 635041). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |