Variant chr19-33387291-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000285.4(PEPD):c.*53C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00342 in 1,608,558 control chromosomes in the GnomAD database, including 200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 11 hom., cov: 33)

Exomes 𝑓: 0.0034 ( 189 hom. )

Consequence

PEPD
NM_000285.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.10

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 19-33387291-G-A is Benign according to our data. Variant chr19-33387291-G-A is described in ClinVar as [Benign]. Clinvar id is 328780.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
PEPD	NM_000285.4 linkuse as main transcript	c.*53C>T	3_prime_UTR_variant	15/15	ENST00000244137.12
PEPD	NM_001166056.2 linkuse as main transcript	c.*53C>T	3_prime_UTR_variant	13/13
PEPD	NM_001166057.2 linkuse as main transcript	c.*53C>T	3_prime_UTR_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEPD	ENST00000244137.12 linkuse as main transcript	c.*53C>T		3_prime_UTR_variant	15/15	1	NM_000285.4	P1	P12955-1

Frequencies

GnomAD3 genomes

AF:

0.00371

AC:

565

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0784

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00903

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000661

Gnomad OTH

AF:

0.00287

GnomAD4 exome

AF:

0.00339

AC:

4939

AN:

1456264

Hom.:

189

Cov.:

AF XY:

0.00334

AC XY:

2421

AN XY:

724040

show subpopulations

Gnomad4 AFR exome

AF:

0.0000898

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.0939

Gnomad4 SAS exome

AF:

0.000581

Gnomad4 FIN exome

AF:

0.0114

Gnomad4 NFE exome

AF:

0.000337

Gnomad4 OTH exome

AF:

0.00317

GnomAD4 genome

AF:

0.00370

AC:

564

AN:

152294

Hom.:

Cov.:

AF XY:

0.00457

AC XY:

340

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0784

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00903

Gnomad4 NFE

AF:

0.000661

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00154

Hom.:

Bravo

AF:

0.00306

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Prolidase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.2

DANN

Benign

0.56

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over