rs10500265

Variant names:

• chr19-33423379-C-G
• rs10500265
• NM_000285.4:c.672-9736G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000285.4(PEPD):​c.672-9736G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0732 in 152,300 control chromosomes in the GnomAD database, including 475 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 0.073 (475 hom., cov: 33)
• Consequence: PEPD NM_000285.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0957 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000285.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEPD	NM_000285.4	MANE Select	c.672-9736G>C		intron	N/A	NP_000276.2
	PEPD	NM_001166056.2		c.549-9736G>C		intron	N/A	NP_001159528.1
	PEPD	NM_001166057.2		c.480-9736G>C		intron	N/A	NP_001159529.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEPD	ENST00000244137.12	TSL:1 MANE Select	c.672-9736G>C		intron	N/A	ENSP00000244137.5
	PEPD	ENST00000651901.2		c.672-9736G>C		intron	N/A	ENSP00000498922.2
	PEPD	ENST00000588328.7	TSL:3	c.672-9736G>C		intron	N/A	ENSP00000468516.4

Frequencies

GnomAD3 genomes AF: 0.0732 AC: 11137 AN: 152182 Hom.: 471 Cov.: 33

Gnomad AFR AF: 0.0435

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0641

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.0229

Gnomad SAS AF: 0.0317

Gnomad FIN AF: 0.0696

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0977

Gnomad OTH AF: 0.0761

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

GnomAD4 genome AF: 0.0732 AC: 11149 AN: 152300 Hom.: 475 Cov.: 33 AF XY: 0.0706 AC XY: 5259 AN XY: 74454

African (AFR) AF: 0.0437 AC: 1817 AN: 41560

American (AMR) AF: 0.0641 AC: 981 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 449 AN: 3466

East Asian (EAS) AF: 0.0227 AC: 118 AN: 5190

South Asian (SAS) AF: 0.0319 AC: 154 AN: 4830

European-Finnish (FIN) AF: 0.0696 AC: 738 AN: 10598

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0977 AC: 6644 AN: 68034

Other (OTH) AF: 0.0753 AC: 159 AN: 2112

Alfa AF: 0.0840 Hom.: 75

Bravo AF: 0.0722

Asia WGS AF: 0.0240 AC: 84 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.2
DANN	Benign	0.39
PhyloP100		0.025
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: rs10500265; hg19: chr19-33914285;