Variant chr15-98968557-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001167902.2(PGPEP1L):c.350T>A(p.Leu117Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PGPEP1L
NM_001167902.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.53

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.943

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGPEP1L	NM_001167902.2 linkuse as main transcript	c.350T>A	p.Leu117Gln	missense_variant	5/5	ENST00000535714.2	NP_001161374.1	A6NFU8-2
PGPEP1L	NM_001102612.2 linkuse as main transcript	c.512T>A	p.Leu171Gln	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.350T>A	p.Leu117Gln	missense_variant	5/5	2	NM_001167902.2	ENSP00000437560.1	A6NFU8-2
PGPEP1L	ENST00000378919.6 linkuse as main transcript	c.512T>A	p.Leu171Gln	missense_variant	5/5	1		ENSP00000368199.6	A6NFU8-1
PGPEP1L	ENST00000637120.2 linkuse as main transcript	c.578T>A	p.Leu193Gln	missense_variant	5/5	5		ENSP00000490927.2	A0A1B0GWH3
SYNM-AS1	ENST00000559468.1 linkuse as main transcript	n.267-2487T>A		intron_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461176

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726776

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:

0.0000375

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 27, 2024

The c.512T>A (p.L171Q) alteration is located in exon 5 (coding exon 4) of the PGPEP1L gene. This alteration results from a T to A substitution at nucleotide position 512, causing the leucine (L) at amino acid position 171 to be replaced by a glutamine (Q). 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

0.31

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.14

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

.;T;.

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.76

T;T;T

M_CAP

Benign

0.032

MetaRNN

Pathogenic

0.94

D;D;D

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.4

.;M;.

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-5.7

D;D;.

REVEL

Uncertain

0.63

Sift

Pathogenic

0.0

D;D;.

Sift4G

Pathogenic

0.0

D;D;.

Polyphen

1.0

.;D;.

Vest4

0.91

MutPred

0.73

.;Loss of catalytic residue at L171 (P = 0.0062);.;

MVP

0.40

MPC

0.31

ClinPred

1.0

GERP RS

5.4

Varity_R

0.86

gMVP

0.42

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over