Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000000068 | SCV005184612 | pathogenic | Nephronophthisis-like nephropathy 1 | 2024-05-24 | criteria provided, single submitter | clinical testing | Variant summary: XPNPEP3 c.1357G>T (p.Gly453Cys) results in a non-conservative amino acid change located in the Peptidase M24 domain (IPR000994) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. Several computational tools predict a significant impact on normal splicing: Four predict the variant weakens a 5' donor site. At least one publication reports experimental evidence that this variant affects mRNA splicing, resulting in the inclusion of 31 nucleotides from intron 9 (O'Toole_2010). The variant allele was found at a frequency of 2.4e-05 in 1613860 control chromosomes in the gnomAD database, including 1 homozygote. This frequency is not significantly higher than estimated for a pathogenic variant in XPNPEP3 causing Nephronophthisis-Like Nephropathy 1, allowing no conclusion about variant significance. c.1357G>T has been reported in the literature in multiple homozygous individuals from a family affected with Nephronophthisis-Like Nephropathy 1 (O'Toole_2010). These data indicate that the variant is very likely to be associated with disease. The following publication has been ascertained in the context of this evaluation (PMID: 20179356). ClinVar contains an entry for this variant (Variation ID: 51). Based on the evidence outlined above, the variant was classified as pathogenic. |
| OMIM | RCV000000068 | SCV000020211 | pathogenic | Nephronophthisis-like nephropathy 1 | 2010-03-01 | no assertion criteria provided | literature only |