Variant chr6-138107166-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_022121.5(PERP):c.175G>A(p.Gly59Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00311 in 1,611,350 control chromosomes in the GnomAD database, including 12 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 11 hom. )

Consequence

PERP
NM_022121.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.551

Variant links:

Genes affected

PERP (HGNC:17637): (p53 apoptosis effector related to PMP22) Involved in activation of cysteine-type endopeptidase activity. Predicted to be located in plasma membrane. Predicted to be active in cell-cell junction. Implicated in erythrokeratodermia variabilis and mutilating palmoplantar keratoderma with periorificial keratotic plaques. [provided by Alliance of Genome Resources, Apr 2022]

PERP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008643001).

BP6

Variant 6-138107166-C-T is Benign according to our data. Variant chr6-138107166-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2656936.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00215 (328/152258) while in subpopulation NFE AF= 0.00397 (270/68014). AF 95% confidence interval is 0.00358. There are 1 homozygotes in gnomad4. There are 136 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 11 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PERP	NM_022121.5 linkuse as main transcript	c.175G>A	p.Gly59Arg	missense_variant	1/3	ENST00000421351.4	NP_071404.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PERP	ENST00000421351.4 linkuse as main transcript	c.175G>A	p.Gly59Arg	missense_variant	1/3	1	NM_022121.5	ENSP00000397157	P1

Frequencies

GnomAD3 genomes

AF:

0.00216

AC:

328

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00397

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00229

AC:

554

AN:

242046

Hom.:

AF XY:

0.00217

AC XY:

288

AN XY:

132530

show subpopulations

Gnomad AFR exome

AF:

0.000597

Gnomad AMR exome

AF:

0.00108

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000887

Gnomad FIN exome

AF:

0.00204

Gnomad NFE exome

AF:

0.00397

Gnomad OTH exome

AF:

0.00184

GnomAD4 exome

AF:

0.00321

AC:

4685

AN:

1459092

Hom.:

Cov.:

AF XY:

0.00307

AC XY:

2230

AN XY:

725894

show subpopulations

Gnomad4 AFR exome

AF:

0.000569

Gnomad4 AMR exome

AF:

0.00101

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000905

Gnomad4 FIN exome

AF:

0.00346

Gnomad4 NFE exome

AF:

0.00377

Gnomad4 OTH exome

AF:

0.00265

GnomAD4 genome

AF:

0.00215

AC:

328

AN:

152258

Hom.:

Cov.:

AF XY:

0.00183

AC XY:

136

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.000578

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00397

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00339

Hom.:

Bravo

AF:

0.00210

ESP6500AA

AF:

0.000683

AC:

ESP6500EA

AF:

0.00303

AC:

ExAC

AF:

0.00256

AC:

310

Asia WGS

AF:

0.000289

AC:

AN:

3476

EpiCase

AF:

0.00371

EpiControl

AF:

0.00296

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PERP-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 31, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

PERP: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Uncertain

0.48

Eigen

Benign

-0.030

Eigen_PC

Benign

-0.092

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.71

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.0086

MetaSVM

Uncertain

-0.13

MutationAssessor

Benign

0.20

MutationTaster

Benign

1.0

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.81

REVEL

Uncertain

0.43

Sift

Benign

0.62

Sift4G

Benign

0.55

Polyphen

1.0

Vest4

0.24

MutPred

0.19

Loss of helix (P = 0.0304);

MVP

0.70

MPC

0.63

ClinPred

0.052

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.19

gMVP

0.63

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