NM_000285.4:c.*175_*178dupATTA

Variant names:

• chr19-33387165-G-GTAAT
• rs16426
• NM_000285.4:c.*175_*178dupATTA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000285.4(PEPD):​c.*175_*178dupATTA 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
• Publications: 5 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: G2P, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEPD	NM_000285.4	MANE Select	c.*175_*178dupATTA		3_prime_UTR	Exon 15 of 15	NP_000276.2	A0A140VJR2
	PEPD	NM_001166056.2		c.*175_*178dupATTA		3_prime_UTR	Exon 13 of 13	NP_001159528.1	P12955-2
	PEPD	NM_001166057.2		c.*175_*178dupATTA		3_prime_UTR	Exon 13 of 13	NP_001159529.1	P12955-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEPD	ENST00000244137.12	TSL:1 MANE Select	c.*175_*178dupATTA		3_prime_UTR	Exon 15 of 15	ENSP00000244137.5	P12955-1
	PEPD	ENST00000651901.2		c.*175_*178dupATTA		3_prime_UTR	Exon 16 of 16	ENSP00000498922.2	A0A494C165
	PEPD	ENST00000588328.7	TSL:3	c.*175_*178dupATTA		3_prime_UTR	Exon 16 of 16	ENSP00000468516.4	K7ES25

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

African (AFR) AF: 0.0308 AC: 424 AN: 13780

American (AMR) AF: 0.269 AC: 5581 AN: 20754

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 1976 AN: 14346

East Asian (EAS) AF: 0.000156 AC: 5 AN: 32036

South Asian (SAS) AF: 0.0553 AC: 2709 AN: 48980

European-Finnish (FIN) AF: 0.168 AC: 5235 AN: 31126

Middle Eastern (MID) AF: 0.129 AC: 264 AN: 2048

European-Non Finnish (NFE) AF: 0.171 AC: 52865 AN: 309820

Other (OTH) AF: 0.148 AC: 4117 AN: 27842

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

African (AFR) AF: 0.0352 AC: 1463 AN: 41542

American (AMR) AF: 0.244 AC: 3727 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 451 AN: 3472

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5172

South Asian (SAS) AF: 0.0564 AC: 272 AN: 4826

European-Finnish (FIN) AF: 0.155 AC: 1642 AN: 10582

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12262 AN: 67946

Other (OTH) AF: 0.168 AC: 354 AN: 2106

Alfa AF: 0.147 Hom.: 214

Bravo AF: 0.139

Asia WGS AF: 0.0370 AC: 129 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Prolidase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.058
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs16426; hg19: chr19-33878071;