rs6510383

Variant names:

• chr19-33427881-T-C
• rs6510383
• NM_000285.4:c.672-14238A>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.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 NM_000285.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360
• Publications: 6 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=-0.93).
• 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 rank	MANE	Protein	UniProt
PEPD	NM_000285.4	c.672-14238A>G		intron_variant	Intron 9 of 14	ENST00000244137.12	NP_000276.2
PEPD	NM_001166056.2	c.549-14238A>G		intron_variant	Intron 7 of 12		NP_001159528.1
PEPD	NM_001166057.2	c.480-14238A>G		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.672-14238A>G		intron_variant	Intron 9 of 14	1	NM_000285.4	ENSP00000244137.5

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

African (AFR) AF: 0.443 AC: 18355 AN: 41476

American (AMR) AF: 0.163 AC: 2498 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 961 AN: 3468

East Asian (EAS) AF: 0.134 AC: 696 AN: 5178

South Asian (SAS) AF: 0.135 AC: 652 AN: 4824

European-Finnish (FIN) AF: 0.232 AC: 2458 AN: 10584

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14761 AN: 67970

Other (OTH) AF: 0.232 AC: 489 AN: 2112

Alfa AF: 0.226 Hom.: 8291

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
PhyloP100		0.036
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: rs6510383; hg19: chr19-33918787;