rs3786897

chr19-33402102-A-Gchr19-33402102-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC124904692 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEPD	NM_000285.4	c.819-233T>C		intron_variant		ENST00000244137.12
LOC124904692	XR_007067229.1	n.234A>G		non_coding_transcript_exon_variant	1/2
PEPD	NM_001166056.2	c.696-233T>C		intron_variant
PEPD	NM_001166057.2	c.627-233T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEPD	ENST00000244137.12	c.819-233T>C		intron_variant		1	NM_000285.4	P1

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

Gnomad4 AFR AF: 0.573

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.427

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.403

Alfa AF: 0.409 Hom.: 14728

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.87
Dann	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs3786897; hg19: chr19-33893008; COSMIC: COSV54888350;