rs731839

Variant names:

• chr19-33408159-G-A
• rs731839
• NM_000285.4:c.818+3513C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-33408159-G-A
• chr19-33408159-G-C
• chr19-33408159-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 125 publications found

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]

PEPD Gene-Disease associations (from GenCC):

• prolidase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)

LOC124904692 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PEPD	NM_000285.4	c.818+3513C>T		intron_variant	Intron 11 of 14	ENST00000244137.12	NP_000276.2
LOC124904692	XR_007067229.1	n.5426G>A		non_coding_transcript_exon_variant	Exon 2 of 2
PEPD	NM_001166056.2	c.695+3513C>T		intron_variant	Intron 9 of 12		NP_001159528.1
PEPD	NM_001166057.2	c.626+3513C>T		intron_variant	Intron 9 of 12		NP_001159529.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEPD	ENST00000244137.12	c.818+3513C>T		intron_variant	Intron 11 of 14	1	NM_000285.4	ENSP00000244137.5

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

African (AFR) AF: 0.626 AC: 26008 AN: 41518

American (AMR) AF: 0.586 AC: 8955 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2130 AN: 3472

East Asian (EAS) AF: 0.430 AC: 2224 AN: 5174

South Asian (SAS) AF: 0.405 AC: 1955 AN: 4826

European-Finnish (FIN) AF: 0.659 AC: 6991 AN: 10616

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.664 AC: 45164 AN: 68002

Other (OTH) AF: 0.619 AC: 1308 AN: 2114

Alfa AF: 0.644 Hom.: 119084

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
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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