rs10425678

chr19-33486490-T-C

Variant summary

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

The NM_000285.4(PEPD):c.503+3506A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 151,774 control chromosomes in the GnomAD database, including 22,739 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 0.53 (22739 hom., cov: 30)
• Consequence: PEPD NM_000285.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEPD	NM_000285.4	c.503+3506A>G		intron_variant		ENST00000244137.12
PEPD	NM_001166056.2	c.503+3506A>G		intron_variant
PEPD	NM_001166057.2	c.311+3506A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEPD	ENST00000244137.12	c.503+3506A>G		intron_variant		1	NM_000285.4	P1

Frequencies

GnomAD3 genomes AF: 0.534 AC: 80990 AN: 151656 Hom.: 22699 Cov.: 30

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.534 AC: 81094 AN: 151774 Hom.: 22739 Cov.: 30 AF XY: 0.531 AC XY: 39353 AN XY: 74132

Gnomad4 AFR AF: 0.705

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.505

Alfa AF: 0.490 Hom.: 23977

Bravo AF: 0.549

Asia WGS AF: 0.322 AC: 1122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.37
Dann	Benign	0.44

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: rs10425678; hg19: chr19-33977396;