Variant rs2715423 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001167902.2(PGPEP1L):c.263C>T(p.Ala88Val) variant causes a missense change. The variant allele was found at a frequency of 0.255 in 1,595,292 control chromosomes in the GnomAD database, including 55,222 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 0.21 ( 3927 hom., cov: 33)

Exomes 𝑓: 0.26 ( 51295 hom. )

Consequence

PGPEP1L
NM_001167902.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.25

Variant links:

Genes affected

PGPEP1L (HGNC:27080): (pyroglutamyl-peptidase I like) Predicted to enable pyroglutamyl-peptidase activity. Predicted to be involved in proteolysis. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

PGPEP1L links:

SYNM-AS1 (HGNC:):

SYNM-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00658828).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGPEP1L	NM_001167902.2 linkuse as main transcript	c.263C>T	p.Ala88Val	missense_variant	5/5	ENST00000535714.2	NP_001161374.1	A6NFU8-2
PGPEP1L	NM_001102612.2 linkuse as main transcript	c.425C>T	p.Ala142Val	missense_variant	5/5		NP_001096082.2	A6NFU8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PGPEP1L	ENST00000535714.2 linkuse as main transcript	c.263C>T	p.Ala88Val	missense_variant	5/5	2	NM_001167902.2	ENSP00000437560.1	A6NFU8-2
PGPEP1L	ENST00000378919.6 linkuse as main transcript	c.425C>T	p.Ala142Val	missense_variant	5/5	1		ENSP00000368199.6	A6NFU8-1
PGPEP1L	ENST00000637120.2 linkuse as main transcript	c.491C>T	p.Ala164Val	missense_variant	5/5	5		ENSP00000490927.2	A0A1B0GWH3
SYNM-AS1	ENST00000559468.1 linkuse as main transcript	n.267-2574C>T		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.208

AC:

31610

AN:

152084

Hom.:

3925

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0907

Gnomad AMI

AF:

0.362

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.212

Gnomad EAS

AF:

0.0669

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.303

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.280

Gnomad OTH

AF:

0.204

GnomAD3 exomes

AF:

0.228

AC:

49869

AN:

218726

Hom.:

6230

AF XY:

0.228

AC XY:

26838

AN XY:

117770

show subpopulations

Gnomad AFR exome

AF:

0.0877

Gnomad AMR exome

AF:

0.202

Gnomad ASJ exome

AF:

0.208

Gnomad EAS exome

AF:

0.0693

Gnomad SAS exome

AF:

0.144

Gnomad FIN exome

AF:

0.309

Gnomad NFE exome

AF:

0.289

Gnomad OTH exome

AF:

0.242

GnomAD4 exome

AF:

0.259

AC:

374451

AN:

1443090

Hom.:

51295

Cov.:

AF XY:

0.257

AC XY:

183887

AN XY:

715900

show subpopulations

Gnomad4 AFR exome

AF:

0.0857

Gnomad4 AMR exome

AF:

0.201

Gnomad4 ASJ exome

AF:

0.209

Gnomad4 EAS exome

AF:

0.0527

Gnomad4 SAS exome

AF:

0.144

Gnomad4 FIN exome

AF:

0.307

Gnomad4 NFE exome

AF:

0.284

Gnomad4 OTH exome

AF:

0.234

GnomAD4 genome

AF:

0.208

AC:

31602

AN:

152202

Hom.:

3927

Cov.:

AF XY:

0.206

AC XY:

15323

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0904

Gnomad4 AMR

AF:

0.206

Gnomad4 ASJ

AF:

0.212

Gnomad4 EAS

AF:

0.0663

Gnomad4 SAS

AF:

0.127

Gnomad4 FIN

AF:

0.303

Gnomad4 NFE

AF:

0.280

Gnomad4 OTH

AF:

0.202

Alfa

AF:

0.253

Hom.:

8605

Bravo

AF:

0.196

TwinsUK

AF:

0.287

AC:

1063

ALSPAC

AF:

0.293

AC:

1130

ESP6500AA

AF:

0.0927

AC:

370

ESP6500EA

AF:

0.273

AC:

2266

ExAC

AF:

0.211

AC:

25400

Asia WGS

AF:

0.134

AC:

467

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.069

.;T;.

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.74

T;T;T

MetaRNN

Benign

0.0066

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.9

.;L;.

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.1

D;D;.

REVEL

Benign

0.12

Sift

Uncertain

0.0090

D;D;.

Sift4G

Benign

0.19

T;T;.

Polyphen

0.16

.;B;.

Vest4

0.15

MPC

0.10

ClinPred

0.041

GERP RS

3.2

Varity_R

0.23

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over