Variant 15-98969491-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001167902.2(PGPEP1L):c.143T>C(p.Met48Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,930 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

PGPEP1L
NM_001167902.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.58

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGPEP1L	NM_001167902.2 linkuse as main transcript	c.143T>C	p.Met48Thr	missense_variant	4/5	ENST00000535714.2	NP_001161374.1	A6NFU8-2
PGPEP1L	NM_001102612.2 linkuse as main transcript	c.305T>C	p.Met102Thr	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.143T>C	p.Met48Thr	missense_variant	4/5	2	NM_001167902.2	ENSP00000437560.1	A6NFU8-2
PGPEP1L	ENST00000378919.6 linkuse as main transcript	c.305T>C	p.Met102Thr	missense_variant	4/5	1		ENSP00000368199.6	A6NFU8-1
PGPEP1L	ENST00000637120.2 linkuse as main transcript	c.371T>C	p.Met124Thr	missense_variant	4/5	5		ENSP00000490927.2	A0A1B0GWH3
SYNM-AS1	ENST00000559468.1 linkuse as main transcript	n.267-3421T>C		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249508

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135208

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461700

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Nov 21, 2024

The c.305T>C (p.M102T) alteration is located in exon 4 (coding exon 3) of the PGPEP1L gene. This alteration results from a T to C substitution at nucleotide position 305, causing the methionine (M) at amino acid position 102 to be replaced by a threonine (T). 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

0.60

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

.;T;.

Eigen

Benign

-0.057

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.39

T;T;T

M_CAP

Benign

0.0061

MetaRNN

Uncertain

0.68

D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

.;M;.

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-5.4

D;D;.

REVEL

Benign

0.10

Sift

Uncertain

0.0050

D;D;.

Sift4G

Uncertain

0.0080

D;T;.

Polyphen

0.69

.;P;.

Vest4

0.52

MutPred

0.68

.;Gain of methylation at K103 (P = 0.0326);.;

MVP

0.11

MPC

0.088

ClinPred

0.92

GERP RS

2.1

Varity_R

0.52

gMVP

0.49

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