Variant 15-98969533-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001167902.2(PGPEP1L):c.101G>A(p.Cys34Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000248 in 1,614,024 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00012 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

PGPEP1L
NM_001167902.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.32

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 Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.901

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGPEP1L	NM_001167902.2 linkuse as main transcript	c.101G>A	p.Cys34Tyr	missense_variant	4/5	ENST00000535714.2	NP_001161374.1	A6NFU8-2
PGPEP1L	NM_001102612.2 linkuse as main transcript	c.263G>A	p.Cys88Tyr	missense_variant	4/5		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.101G>A	p.Cys34Tyr	missense_variant	4/5	2	NM_001167902.2	ENSP00000437560.1	A6NFU8-2
PGPEP1L	ENST00000378919.6 linkuse as main transcript	c.263G>A	p.Cys88Tyr	missense_variant	4/5	1		ENSP00000368199.6	A6NFU8-1
PGPEP1L	ENST00000637120.2 linkuse as main transcript	c.329G>A	p.Cys110Tyr	missense_variant	4/5	5		ENSP00000490927.2	A0A1B0GWH3
SYNM-AS1	ENST00000559468.1 linkuse as main transcript	n.267-3463G>A		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000313

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000481

AC:

AN:

249352

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135218

show subpopulations

Gnomad AFR exome

AF:

0.000192

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000501

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1461658

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000118

AC:

AN:

152366

Hom.:

Cov.:

AF XY:

0.000174

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000128

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2024

The c.263G>A (p.C88Y) alteration is located in exon 4 (coding exon 3) of the PGPEP1L gene. This alteration results from a G to A substitution at nucleotide position 263, causing the cysteine (C) at amino acid position 88 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

.;T;.

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.77

T;T;T

M_CAP

Benign

0.015

MetaRNN

Pathogenic

0.90

D;D;D

MetaSVM

Benign

-0.36

MutationAssessor

Pathogenic

3.2

.;M;.

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-11

D;D;.

REVEL

Uncertain

0.43

Sift

Uncertain

0.0010

D;D;.

Sift4G

Uncertain

0.044

D;D;.

Polyphen

1.0

.;D;.

Vest4

0.90

MutPred

0.77

.;Gain of phosphorylation at C88 (P = 0.0434);.;

MVP

0.48

MPC

0.38

ClinPred

0.96

GERP RS

4.4

Varity_R

0.96

gMVP

0.51

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over