NM_017712.4:c.325_327delGTGinsTTA

Variant names:

• chr19-18357503-GTG-TTA
• NM_017712.4:c.325_327delGTGinsTTA
• PGPEP1 p.Val109Leu

Variant summary

Our verdict is

Uncertain significance

0 Uncertain · Cold

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

. The variant received 0 ACMG points: 0P and 0B.

The NM_017712.4(PGPEP1):​c.325_327delGTGinsTTA​(p.Val109Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V109M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PGPEP1 NM_017712.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.39
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017712.4. 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
	PGPEP1	NM_017712.4	MANE Select	c.325_327delGTGinsTTA	p.Val109Leu	missense	N/A	NP_060182.1	Q9NXJ5-1
	PGPEP1	NM_001329471.2		c.325_327delGTGinsTTA	p.Val109Leu	missense	N/A	NP_001316400.1
	PGPEP1	NM_001308366.2		c.325_327delGTGinsTTA	p.Val109Leu	missense	N/A	NP_001295295.1	S4R2Y9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGPEP1	ENST00000269919.11	TSL:1 MANE Select	c.325_327delGTGinsTTA	p.Val109Leu	missense	N/A	ENSP00000269919.3	Q9NXJ5-1
	PGPEP1	ENST00000596962.5	TSL:1	n.*176_*178delGTGinsTTA		3_prime_UTR	Exon 5 of 6	ENSP00000470622.1	M0QX66
	PGPEP1	ENST00000600283.6	TSL:1	n.*176_*178delGTGinsTTA		3_prime_UTR	Exon 5 of 6	ENSP00000468932.1	M0QX66

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.4

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-18468313;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline