15-98968644-G-A

Variant names:

• chr15-98968644-G-A
• rs2715423
• NM_001167902.2:c.263C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001167902.2(PGPEP1L):​c.263C>T​(p.Ala88Val) variant causes a missense change. The variant allele was found at a frequency of 0.255 in 1,595,292 control chromosomes in the GnomAD database, including 55,222 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A88T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.21 (3927 hom., cov: 33)
  • Exomes 𝑓: 0.26 (51295 hom.)
• Consequence: PGPEP1L NM_001167902.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.25
• Publications: 26 publications found

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:55421): (SYNM antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00658828).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001167902.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGPEP1L	NM_001167902.2	MANE Select	c.263C>T	p.Ala88Val	missense	Exon 5 of 5	NP_001161374.1
	PGPEP1L	NM_001102612.2		c.425C>T	p.Ala142Val	missense	Exon 5 of 5	NP_001096082.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGPEP1L	ENST00000535714.2	TSL:2 MANE Select	c.263C>T	p.Ala88Val	missense	Exon 5 of 5	ENSP00000437560.1
	PGPEP1L	ENST00000378919.6	TSL:1	c.425C>T	p.Ala142Val	missense	Exon 5 of 5	ENSP00000368199.6
	PGPEP1L	ENST00000637120.2	TSL:5	c.491C>T	p.Ala164Val	missense	Exon 5 of 5	ENSP00000490927.2

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31610 AN: 152084 Hom.: 3925 Cov.: 33

Gnomad AFR AF: 0.0907

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0669

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.204

GnomAD2 exomes AF: 0.228 AC: 49869 AN: 218726 AF XY: 0.228

Gnomad AFR exome AF: 0.0877

Gnomad AMR exome AF: 0.202

Gnomad ASJ exome AF: 0.208

Gnomad EAS exome AF: 0.0693

Gnomad FIN exome AF: 0.309

Gnomad NFE exome AF: 0.289

Gnomad OTH exome AF: 0.242

GnomAD4 exome AF: 0.259 AC: 374451 AN: 1443090 Hom.: 51295 Cov.: 41 AF XY: 0.257 AC XY: 183887 AN XY: 715900

African (AFR) AF: 0.0857 AC: 2849 AN: 33248

American (AMR) AF: 0.201 AC: 8322 AN: 41486

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 5377 AN: 25760

East Asian (EAS) AF: 0.0527 AC: 2055 AN: 39014

South Asian (SAS) AF: 0.144 AC: 11965 AN: 83228

European-Finnish (FIN) AF: 0.307 AC: 16064 AN: 52284

Middle Eastern (MID) AF: 0.196 AC: 1127 AN: 5742

European-Non Finnish (NFE) AF: 0.284 AC: 312677 AN: 1102506

Other (OTH) AF: 0.234 AC: 14015 AN: 59822

GnomAD4 genome AF: 0.208 AC: 31602 AN: 152202 Hom.: 3927 Cov.: 33 AF XY: 0.206 AC XY: 15323 AN XY: 74410

African (AFR) AF: 0.0904 AC: 3757 AN: 41546

American (AMR) AF: 0.206 AC: 3147 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 736 AN: 3470

East Asian (EAS) AF: 0.0663 AC: 344 AN: 5186

South Asian (SAS) AF: 0.127 AC: 612 AN: 4820

European-Finnish (FIN) AF: 0.303 AC: 3203 AN: 10578

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19006 AN: 67998

Other (OTH) AF: 0.202 AC: 426 AN: 2110

Alfa AF: 0.251 Hom.: 17809

Bravo AF: 0.196

TwinsUK AF: 0.287 AC: 1063

ALSPAC AF: 0.293 AC: 1130

ESP6500AA AF: 0.0927 AC: 370

ESP6500EA AF: 0.273 AC: 2266

ExAC AF: 0.211 AC: 25400

Asia WGS AF: 0.134 AC: 467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0066	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.9	L
PhyloP100		5.3
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.12
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.19	T
Polyphen		0.16	B
Vest4		0.15
MPC		0.10
ClinPred		0.041	T
GERP RS		3.2
Varity_R		0.23
gMVP		0.33
Mutation Taster		=86/14	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2715423; hg19: chr15-99511873; COSMIC: COSV51270468; COSMIC: COSV51270468;