NM_000285.4:c.819-233T>C

Variant names:

• chr19-33402102-A-G
• rs3786897
• NM_000285.4:c.819-233T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000285.4(PEPD):​c.819-233T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 152,022 control chromosomes in the GnomAD database, including 15,664 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.44 (15664 hom., cov: 33)
• Consequence: PEPD NM_000285.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.220
• Publications: 101 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)

LOC124904692 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 19-33402102-A-G is Benign according to our data. Variant chr19-33402102-A-G is described in ClinVar as Benign. ClinVar VariationId is 1276572.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.567 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.819-233T>C		intron	N/A	NP_000276.2
	PEPD	NM_001166056.2		c.696-233T>C		intron	N/A	NP_001159528.1
	PEPD	NM_001166057.2		c.627-233T>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.819-233T>C		intron	N/A	ENSP00000244137.5
	PEPD	ENST00000651901.2		c.819-233T>C		intron	N/A	ENSP00000498922.2
	PEPD	ENST00000588328.7	TSL:3	c.819-233T>C		intron	N/A	ENSP00000468516.4

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67335 AN: 151904 Hom.: 15652 Cov.: 33

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.443 AC: 67380 AN: 152022 Hom.: 15664 Cov.: 33 AF XY: 0.435 AC XY: 32355 AN XY: 74310

African (AFR) AF: 0.573 AC: 23760 AN: 41470

American (AMR) AF: 0.293 AC: 4478 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1501 AN: 3470

East Asian (EAS) AF: 0.420 AC: 2166 AN: 5154

South Asian (SAS) AF: 0.265 AC: 1278 AN: 4820

European-Finnish (FIN) AF: 0.427 AC: 4519 AN: 10580

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28386 AN: 67926

Other (OTH) AF: 0.403 AC: 851 AN: 2112

Alfa AF: 0.418 Hom.: 44486

Bravo AF: 0.442

Asia WGS AF: 0.358 AC: 1245 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.87
DANN	Benign	0.69
PhyloP100		-0.22
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: rs3786897; hg19: chr19-33893008; COSMIC: COSV54888350;