Submissions for variant NM_022098.4(XPNPEP3):c.577C>T (p.Pro193Ser)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV004485614	SCV004979729	uncertain significance	Inborn genetic diseases	2023-11-18	criteria provided, single submitter	clinical testing	The c.577C>T (p.P193S) alteration is located in exon 3 (coding exon 3) of the XPNPEP3 gene. This alteration results from a C to T substitution at nucleotide position 577, causing the proline (P) at amino acid position 193 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Neuberg Centre For Genomic Medicine, NCGM	RCV004771550	SCV005382487	uncertain significance	Nephronophthisis-like nephropathy 1	2023-05-20	criteria provided, single submitter	clinical testing	The observed missense variant c.577C>T(p.Pro193Ser) in XPNPEP3 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.577C>T variant has 0.001% allele frequency in gnomAD Exomes. The amino acid Proline at position 193 is changed to a Serine changing protein sequence and it might alter its composition and physico-chemical properties. Multiple lines of computational evidence (Polyphen, SIFT and Mutation Taster) predict no damaging effect on protein structure and function for this variant.The reference amino acid change in XPNPEP3 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.