19-33408159-G-A

Position:

• chr19-33408159-G-A

Variant summary

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

The NM_000285.4(PEPD):​c.818+3513C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 152,222 control chromosomes in the GnomAD database, including 30,302 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 0.63 (30302 hom., cov: 35)
• Consequence: PEPD NM_000285.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.931

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]

LOC124904692 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEPD	NM_000285.4	c.818+3513C>T		intron_variant		ENST00000244137.12	NP_000276.2
LOC124904692	XR_007067229.1	n.5426G>A		non_coding_transcript_exon_variant	2/2
PEPD	NM_001166056.2	c.695+3513C>T		intron_variant			NP_001159528.1
PEPD	NM_001166057.2	c.626+3513C>T		intron_variant			NP_001159529.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEPD	ENST00000244137.12	c.818+3513C>T		intron_variant		1	NM_000285.4	ENSP00000244137	P1

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95371 AN: 152104 Hom.: 30264 Cov.: 35

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.627 AC: 95472 AN: 152222 Hom.: 30302 Cov.: 35 AF XY: 0.621 AC XY: 46233 AN XY: 74426

Gnomad4 AFR AF: 0.626

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.659

Gnomad4 NFE AF: 0.664

Gnomad4 OTH AF: 0.619

Alfa AF: 0.644 Hom.: 44859

Bravo AF: 0.628

Asia WGS AF: 0.436 AC: 1520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.16
DANN	Benign	0.42

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: rs731839; hg19: chr19-33899065; COSMIC: COSV54888385;