19-18369799-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017712.4(PGPEP1):c.*6216C>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 0.271 in 151,968 control chromosomes in the GnomAD database, including 5,738 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (5737 hom., cov: 31)
  • Exomes 𝑓: 0.22 (1 hom.)
• Consequence: PGPEP1 NM_017712.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.262

Genes affected

PGPEP1 (HGNC:13568): (pyroglutamyl-peptidase I) The gene encodes a cysteine protease and member of the peptidase C15 family of proteins. The encoded protein cleaves amino terminal pyroglutamate residues from protein substrates including thyrotropin-releasing hormone and other neuropeptides. Expression of this gene may be downregulated in colorectal cancer, while activity of the encoded protein may be negatively correlated with cancer progression in colorectal cancer patients. Activity of the encoded protease may also be altered in other disease states including in liver cirrhosis, which is associated with reduced protease activity, and in necrozoospermia, which is associated with elevated protease activity. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGPEP1	NM_017712.4	c.*6216C>T		3_prime_UTR_variant	5/5	ENST00000269919.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGPEP1	ENST00000269919.11	c.*6216C>T		3_prime_UTR_variant	5/5	1	NM_017712.4	P1
PGPEP1	ENST00000597663.2	c.234C>T	p.Pro78=	synonymous_variant	2/2	3
PGPEP1	ENST00000595552.2	c.*5C>T		3_prime_UTR_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41031 AN: 151796 Hom.: 5718 Cov.: 31

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.248

GnomAD3 exomes AF: 0.245 AC: 600 AN: 2448 Hom.: 76 AF XY: 0.240 AC XY: 266 AN XY: 1108

Gnomad ASJ exome AF: 0.300

Gnomad NFE exome AF: 0.246

Gnomad OTH exome AF: 0.0625

GnomAD4 exome AF: 0.222 AC: 12 AN: 54 Hom.: 1 Cov.: 0 AF XY: 0.273 AC XY: 12 AN XY: 44

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.208

GnomAD4 genome AF: 0.271 AC: 41096 AN: 151914 Hom.: 5737 Cov.: 31 AF XY: 0.275 AC XY: 20414 AN XY: 74234

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.247

Alfa AF: 0.235 Hom.: 6260

Bravo AF: 0.278

Asia WGS AF: 0.280 AC: 975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.8
Dann	Benign	0.55

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: rs7226; hg19: chr19-18480609;