19-33418804-T-G

Variant names:

• chr19-33418804-T-G
• rs8182584
• NM_000285.4:c.672-5161A>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.672-5161A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 152,062 control chromosomes in the GnomAD database, including 26,685 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 0.59 (26685 hom., cov: 33)
• Consequence: PEPD NM_000285.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46
• Publications: 59 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 (NFE) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEPD	NM_000285.4	c.672-5161A>C		intron_variant	Intron 9 of 14	ENST00000244137.12	NP_000276.2
PEPD	NM_001166056.2	c.549-5161A>C		intron_variant	Intron 7 of 12		NP_001159528.1
PEPD	NM_001166057.2	c.480-5161A>C		intron_variant	Intron 7 of 12		NP_001159529.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEPD	ENST00000244137.12	c.672-5161A>C		intron_variant	Intron 9 of 14	1	NM_000285.4	ENSP00000244137.5

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89426 AN: 151944 Hom.: 26655 Cov.: 33

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.589 AC: 89510 AN: 152062 Hom.: 26685 Cov.: 33 AF XY: 0.583 AC XY: 43313 AN XY: 74350

African (AFR) AF: 0.606 AC: 25125 AN: 41468

American (AMR) AF: 0.561 AC: 8578 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1823 AN: 3466

East Asian (EAS) AF: 0.348 AC: 1798 AN: 5166

South Asian (SAS) AF: 0.371 AC: 1786 AN: 4818

European-Finnish (FIN) AF: 0.606 AC: 6407 AN: 10572

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.619 AC: 42107 AN: 67972

Other (OTH) AF: 0.570 AC: 1203 AN: 2112

Alfa AF: 0.597 Hom.: 54909

Bravo AF: 0.592

Asia WGS AF: 0.375 AC: 1306 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.012
DANN	Benign	0.32
PhyloP100		-2.5
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: rs8182584; hg19: chr19-33909710;