Variant chr6-138107216-C-A 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.125G>T(p.Gly42Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,612,444 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0085 ( 22 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 25 hom. )

Consequence

PERP
NM_022121.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.843

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=0.0025757253).

BP6

Variant 6-138107216-C-A is Benign according to our data. Variant chr6-138107216-C-A is described in ClinVar as [Benign]. Clinvar id is 792057.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00848 (1291/152324) while in subpopulation AFR AF= 0.029 (1205/41568). AF 95% confidence interval is 0.0276. There are 22 homozygotes in gnomad4. There are 639 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 22 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PERP	NM_022121.5 linkuse as main transcript	c.125G>T	p.Gly42Val	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.125G>T	p.Gly42Val	missense_variant	1/3	1	NM_022121.5	ENSP00000397157	P1

Frequencies

GnomAD3 genomes

AF:

0.00839

AC:

1277

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0287

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00197

AC:

480

AN:

243820

Hom.:

AF XY:

0.00162

AC XY:

216

AN XY:

133408

show subpopulations

Gnomad AFR exome

AF:

0.0271

Gnomad AMR exome

AF:

0.00131

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000984

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000147

Gnomad OTH exome

AF:

0.000997

GnomAD4 exome

AF:

0.00103

AC:

1510

AN:

1460120

Hom.:

Cov.:

AF XY:

0.000918

AC XY:

667

AN XY:

726412

show subpopulations

Gnomad4 AFR exome

AF:

0.0303

Gnomad4 AMR exome

AF:

0.00166

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000146

Gnomad4 OTH exome

AF:

0.00394

GnomAD4 genome

AF:

0.00848

AC:

1291

AN:

152324

Hom.:

Cov.:

AF XY:

0.00858

AC XY:

639

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0290

Gnomad4 AMR

AF:

0.00411

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00209

Hom.:

Bravo

AF:

0.00977

ESP6500AA

AF:

0.0238

AC:

104

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00223

AC:

269

Asia WGS

AF:

0.00636

AC:

AN:

3476

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.046

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.063

DANN

Benign

0.56

DEOGEN2

Benign

0.33

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.065

MetaRNN

Benign

0.0026

MetaSVM

Benign

-0.81

MutationAssessor

Benign

-1.3

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

0.90

REVEL

Benign

0.16

Sift

Benign

0.60

Sift4G

Benign

0.39

Polyphen

0.0

Vest4

0.077

MVP

0.25

MPC

0.65

ClinPred

0.0068

GERP RS

-8.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.037

gMVP

0.51

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