rs10425678

Variant names:

• chr19-33486490-T-C
• rs10425678
• NM_000285.4:c.503+3506A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PEPD	NM_000285.4	c.503+3506A>G		intron_variant	Intron 6 of 14	ENST00000244137.12	NP_000276.2
PEPD	NM_001166056.2	c.503+3506A>G		intron_variant	Intron 6 of 12		NP_001159528.1
PEPD	NM_001166057.2	c.311+3506A>G		intron_variant	Intron 4 of 12		NP_001159529.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEPD	ENST00000244137.12	c.503+3506A>G		intron_variant	Intron 6 of 14	1	NM_000285.4	ENSP00000244137.5

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

African (AFR) AF: 0.705 AC: 29188 AN: 41374

American (AMR) AF: 0.508 AC: 7749 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1709 AN: 3470

East Asian (EAS) AF: 0.217 AC: 1109 AN: 5116

South Asian (SAS) AF: 0.319 AC: 1525 AN: 4788

European-Finnish (FIN) AF: 0.508 AC: 5361 AN: 10554

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32743 AN: 67900

Other (OTH) AF: 0.505 AC: 1063 AN: 2104

Alfa AF: 0.493 Hom.: 28712

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
PhyloP100		-1.4
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: rs10425678; hg19: chr19-33977396;