19-33387006-G-GAAAGT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000285.4(PEPD):c.*337_*338insACTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 328,826 control chromosomes in the GnomAD database, including 11,394 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (6378 hom., cov: 21)
  • Exomes 𝑓: 0.22 (5016 hom.)
• Consequence: PEPD NM_000285.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.992

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 19-33387006-G-GAAAGT is Benign according to our data. Variant chr19-33387006-G-GAAAGT is described in ClinVar as [Benign]. Clinvar id is 328776.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEPD	NM_000285.4	c.*337_*338insACTTT		3_prime_UTR_variant	15/15	ENST00000244137.12
PEPD	NM_001166056.2	c.*337_*338insACTTT		3_prime_UTR_variant	13/13
PEPD	NM_001166057.2	c.*337_*338insACTTT		3_prime_UTR_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEPD	ENST00000244137.12	c.*337_*338insACTTT		3_prime_UTR_variant	15/15	1	NM_000285.4	P1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42649 AN: 151802 Hom.: 6368 Cov.: 21

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.260

GnomAD4 exome AF: 0.225 AC: 39736 AN: 176906 Hom.: 5016 Cov.: 0 AF XY: 0.219 AC XY: 20208 AN XY: 92078

Gnomad4 AFR exome AF: 0.379

Gnomad4 AMR exome AF: 0.183

Gnomad4 ASJ exome AF: 0.265

Gnomad4 EAS exome AF: 0.156

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.217

Gnomad4 NFE exome AF: 0.238

Gnomad4 OTH exome AF: 0.234

GnomAD4 genome AF: 0.281 AC: 42679 AN: 151920 Hom.: 6378 Cov.: 21 AF XY: 0.276 AC XY: 20471 AN XY: 74224

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.258

Alfa AF: 0.274 Hom.: 633

Bravo AF: 0.286

Asia WGS AF: 0.185 AC: 643 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Prolidase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs140842; hg19: chr19-33877912;