rs17569
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000285.4(PEPD):c.1131C>T(p.His377=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,610,930 control chromosomes in the GnomAD database, including 18,295 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.11 ( 1256 hom., cov: 34)
Exomes 𝑓: 0.15 ( 17039 hom. )
Consequence
PEPD
NM_000285.4 synonymous
NM_000285.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.612
Genes affected
PEPD (HGNC:8840): (peptidase D) This gene encodes a member of the peptidase family. The protein forms a homodimer that hydrolyzes dipeptides or tripeptides with C-terminal proline or hydroxyproline residues. The enzyme serves an important role in the recycling of proline, and may be rate limiting for the production of collagen. Mutations in this gene result in prolidase deficiency, which is characterized by the excretion of large amount of di- and tri-peptides containing proline. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
Variant 19-33391316-G-A is Benign according to our data. Variant chr19-33391316-G-A is described in ClinVar as [Benign]. Clinvar id is 328799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-33391316-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.612 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PEPD | NM_000285.4 | c.1131C>T | p.His377= | synonymous_variant | 13/15 | ENST00000244137.12 | |
PEPD | NM_001166056.2 | c.1008C>T | p.His336= | synonymous_variant | 11/13 | ||
PEPD | NM_001166057.2 | c.939C>T | p.His313= | synonymous_variant | 11/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PEPD | ENST00000244137.12 | c.1131C>T | p.His377= | synonymous_variant | 13/15 | 1 | NM_000285.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.109 AC: 16606AN: 152082Hom.: 1255 Cov.: 34
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GnomAD3 exomes AF: 0.129 AC: 31540AN: 243920Hom.: 2378 AF XY: 0.132 AC XY: 17542AN XY: 133048
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GnomAD4 exome AF: 0.148 AC: 215804AN: 1458730Hom.: 17039 Cov.: 34 AF XY: 0.147 AC XY: 106752AN XY: 725504
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GnomAD4 genome AF: 0.109 AC: 16598AN: 152200Hom.: 1256 Cov.: 34 AF XY: 0.106 AC XY: 7897AN XY: 74406
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Prolidase deficiency Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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BayesDel_noAF
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CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at