rs121917722
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The NM_000285.4(PEPD):c.551G>A(p.Arg184Gln) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000151 in 1,458,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_000285.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PEPD | NM_000285.4 | c.551G>A | p.Arg184Gln | missense_variant, splice_region_variant | 8/15 | ENST00000244137.12 | |
PEPD | NM_001166057.2 | c.359G>A | p.Arg120Gln | missense_variant, splice_region_variant | 6/13 | ||
PEPD | NM_001166056.2 | c.548+13986G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PEPD | ENST00000244137.12 | c.551G>A | p.Arg184Gln | missense_variant, splice_region_variant | 8/15 | 1 | NM_000285.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000241 AC: 6AN: 248624Hom.: 0 AF XY: 0.0000297 AC XY: 4AN XY: 134864
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1458904Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12AN XY: 725940
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 184 of the PEPD protein (p.Arg184Gln). This variant is present in population databases (rs121917722, gnomAD 0.009%). This missense change has been observed in individual(s) with prolidase deficiency (PMID: 8900231). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 211). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects PEPD function (PMID: 8900231). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. - |
Prolidase deficiency Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 1996 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at