19-33387165-G-GTAAT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000285.4(PEPD):c.*178_*179insATTA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 652,862 control chromosomes in the GnomAD database, including 8,242 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1832 hom., cov: 30)
  • Exomes 𝑓: 0.15 (6410 hom.)
• Consequence: PEPD NM_000285.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0580

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 -16 ACMG points.

• BP6: Variant 19-33387165-G-GTAAT is Benign according to our data. Variant chr19-33387165-G-GTAAT is described in ClinVar as [Benign]. Clinvar id is 328778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEPD	NM_000285.4	c.*178_*179insATTA		3_prime_UTR_variant	15/15	ENST00000244137.12
PEPD	NM_001166056.2	c.*178_*179insATTA		3_prime_UTR_variant	13/13
PEPD	NM_001166057.2	c.*178_*179insATTA		3_prime_UTR_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEPD	ENST00000244137.12	c.*178_*179insATTA		3_prime_UTR_variant	15/15	1	NM_000285.4	P1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20372 AN: 152012 Hom.: 1823 Cov.: 30

Gnomad AFR AF: 0.0353

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0553

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.171

GnomAD4 exome AF: 0.146 AC: 73176 AN: 500732 Hom.: 6410 Cov.: 6 AF XY: 0.140 AC XY: 36892 AN XY: 263282

Gnomad4 AFR exome AF: 0.0308

Gnomad4 AMR exome AF: 0.269

Gnomad4 ASJ exome AF: 0.138

Gnomad4 EAS exome AF: 0.000156

Gnomad4 SAS exome AF: 0.0553

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.171

Gnomad4 OTH exome AF: 0.148

GnomAD4 genome AF: 0.134 AC: 20392 AN: 152130 Hom.: 1832 Cov.: 30 AF XY: 0.133 AC XY: 9916 AN XY: 74376

Gnomad4 AFR AF: 0.0352

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0564

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.168

Alfa AF: 0.147 Hom.: 214

Bravo AF: 0.139

Asia WGS AF: 0.0370 AC: 129 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

- -

Prolidase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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: rs16426; hg19: chr19-33878071;