Variant chr15-98968693-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001167902.2(PGPEP1L):c.214G>A(p.Val72Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000422 in 1,562,134 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000038 ( 1 hom. )

Consequence

PGPEP1L
NM_001167902.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.308

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09079173).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGPEP1L	NM_001167902.2 linkuse as main transcript	c.214G>A	p.Val72Ile	missense_variant	5/5	ENST00000535714.2	NP_001161374.1	A6NFU8-2
PGPEP1L	NM_001102612.2 linkuse as main transcript	c.376G>A	p.Val126Ile	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.214G>A	p.Val72Ile	missense_variant	5/5	2	NM_001167902.2	ENSP00000437560.1	A6NFU8-2
PGPEP1L	ENST00000378919.6 linkuse as main transcript	c.376G>A	p.Val126Ile	missense_variant	5/5	1		ENSP00000368199.6	A6NFU8-1
PGPEP1L	ENST00000637120.2 linkuse as main transcript	c.442G>A	p.Val148Ile	missense_variant	5/5	5		ENSP00000490927.2	A0A1B0GWH3
SYNM-AS1	ENST00000559468.1 linkuse as main transcript	n.267-2623G>A		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000765

AC:

AN:

169898

Hom.:

AF XY:

0.000123

AC XY:

AN XY:

89778

show subpopulations

Gnomad AFR exome

AF:

0.000106

Gnomad AMR exome

AF:

0.0000786

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000343

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000145

Gnomad OTH exome

AF:

0.000211

GnomAD4 exome

AF:

0.0000376

AC:

AN:

1409896

Hom.:

Cov.:

AF XY:

0.0000503

AC XY:

AN XY:

696428

show subpopulations

Gnomad4 AFR exome

AF:

0.000155

Gnomad4 AMR exome

AF:

0.0000545

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000164

Gnomad4 SAS exome

AF:

0.000250

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000138

Gnomad4 OTH exome

AF:

0.0000853

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000322

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000258

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

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

Dec 27, 2023

The c.376G>A (p.V126I) alteration is located in exon 5 (coding exon 4) of the PGPEP1L gene. This alteration results from a G to A substitution at nucleotide position 376, causing the valine (V) at amino acid position 126 to be replaced by an isoleucine (I). 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

Benign

0.11

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.67

CADD

Benign

7.0

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0093

.;T;.

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.80

T;T;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.091

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

.;L;.

PrimateAI

Benign

0.32

PROVEAN

Benign

0.23

N;N;.

REVEL

Benign

0.038

Sift

Benign

0.17

T;T;.

Sift4G

Benign

0.25

T;T;.

Polyphen

0.32

.;B;.

Vest4

0.055

MVP

0.014

MPC

0.049

ClinPred

0.013

GERP RS

0.99

Varity_R

0.058

gMVP

0.065

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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