15-98968651-C-T

Position:

• chr15-98968651-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001167902.2(PGPEP1L):​c.256G>A​(p.Gly86Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PGPEP1L NM_001167902.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28

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]

SYNM-AS1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38239992).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGPEP1L	NM_001167902.2	c.256G>A	p.Gly86Ser	missense_variant	5/5	ENST00000535714.2	NP_001161374.1
PGPEP1L	NM_001102612.2	c.418G>A	p.Gly140Ser	missense_variant	5/5		NP_001096082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGPEP1L	ENST00000535714.2	c.256G>A	p.Gly86Ser	missense_variant	5/5	2	NM_001167902.2	ENSP00000437560.1
PGPEP1L	ENST00000378919.6	c.418G>A	p.Gly140Ser	missense_variant	5/5	1		ENSP00000368199.6
PGPEP1L	ENST00000637120.2	c.484G>A	p.Gly162Ser	missense_variant	5/5	5		ENSP00000490927.2
SYNM-AS1	ENST00000559468.1	n.267-2581G>A		intron_variant		4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2022

The c.418G>A (p.G140S) 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 418, causing the glycine (G) at amino acid position 140 to be replaced by a serine (S). 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	0.21
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	.;T;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.38	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	2.0	.;M;.
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-4.3	D;D;.
REVEL	Benign	0.26
Sift	Benign	0.048	D;T;.
Sift4G	Uncertain	0.060	T;T;.
Polyphen		0.96	.;D;.
Vest4		0.50
MutPred		0.67		.;Gain of helix (P = 0.0854);.;
MVP		0.061
MPC		0.30
ClinPred		0.89	D
GERP RS		3.4
Varity_R		0.31
gMVP		0.32

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.

Other links and lift over

hg19: chr15-99511880;