rs889140

chr19-33398094-G-Achr19-33398094-G-Cchr19-33398094-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000285.4(PEPD):c.967+3627C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 152,112 control chromosomes in the GnomAD database, including 33,877 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (33877 hom., cov: 33)
• Consequence: PEPD NM_000285.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEPD	NM_000285.4	c.967+3627C>T		intron_variant		ENST00000244137.12
PEPD	NM_001166056.2	c.844+3627C>T		intron_variant
PEPD	NM_001166057.2	c.775+3627C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEPD	ENST00000244137.12	c.967+3627C>T		intron_variant		1	NM_000285.4	P1

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100434 AN: 151994 Hom.: 33835 Cov.: 33

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.666

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.661 AC: 100537 AN: 152112 Hom.: 33877 Cov.: 33 AF XY: 0.650 AC XY: 48328 AN XY: 74366

Gnomad4 AFR AF: 0.770

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.659

Alfa AF: 0.649 Hom.: 45984

Bravo AF: 0.674

Asia WGS AF: 0.421 AC: 1469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.1
Dann	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs889140; hg19: chr19-33889000; COSMIC: COSV54896662; COSMIC: COSV54896662;