rs6510383

Positions:

• chr19-33427881-T-C

Variant summary

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

The ENST00000244137.12(PEPD):​c.672-14238A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,104 control chromosomes in the GnomAD database, including 6,550 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 0.27 (6550 hom., cov: 32)
• Consequence: PEPD ENST00000244137.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360

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 = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEPD	NM_000285.4	c.672-14238A>G		intron_variant		ENST00000244137.12	NP_000276.2
PEPD	NM_001166056.2	c.549-14238A>G		intron_variant			NP_001159528.1
PEPD	NM_001166057.2	c.480-14238A>G		intron_variant			NP_001159529.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEPD	ENST00000244137.12	c.672-14238A>G		intron_variant		1	NM_000285.4	ENSP00000244137	P1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41103 AN: 151986 Hom.: 6530 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.271 AC: 41156 AN: 152104 Hom.: 6550 Cov.: 32 AF XY: 0.266 AC XY: 19799 AN XY: 74376

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.232

Alfa AF: 0.220 Hom.: 5673

Bravo AF: 0.275

Asia WGS AF: 0.154 AC: 538 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	5.4
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: rs6510383; hg19: chr19-33918787;