Variant chr6-138107242-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_022121.5(PERP):c.99C>T(p.Arg33=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00947 in 1,612,250 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0075 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0097 ( 80 hom. )

Consequence

PERP
NM_022121.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.21

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 6-138107242-G-A is Benign according to our data. Variant chr6-138107242-G-A is described in ClinVar as [Benign]. Clinvar id is 710628.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.21 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00749 (1141/152324) while in subpopulation NFE AF= 0.0113 (772/68028). AF 95% confidence interval is 0.0107. There are 6 homozygotes in gnomad4. There are 536 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PERP	NM_022121.5 linkuse as main transcript	c.99C>T	p.Arg33=	synonymous_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.99C>T	p.Arg33=	synonymous_variant	1/3	1	NM_022121.5	ENSP00000397157	P1

Frequencies

GnomAD3 genomes

AF:

0.00752

AC:

1144

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.00949

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00931

Gnomad FIN

AF:

0.00452

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.0113

Gnomad OTH

AF:

0.00957

GnomAD3 exomes

AF:

0.00813

AC:

1969

AN:

242312

Hom.:

AF XY:

0.00864

AC XY:

1147

AN XY:

132734

show subpopulations

Gnomad AFR exome

AF:

0.00168

Gnomad AMR exome

AF:

0.00783

Gnomad ASJ exome

AF:

0.00741

Gnomad EAS exome

AF:

0.0000560

Gnomad SAS exome

AF:

0.00785

Gnomad FIN exome

AF:

0.00602

Gnomad NFE exome

AF:

0.0108

Gnomad OTH exome

AF:

0.0112

GnomAD4 exome

AF:

0.00968

AC:

14129

AN:

1459926

Hom.:

Cov.:

AF XY:

0.00970

AC XY:

7042

AN XY:

726310

show subpopulations

Gnomad4 AFR exome

AF:

0.00147

Gnomad4 AMR exome

AF:

0.00848

Gnomad4 ASJ exome

AF:

0.00640

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00820

Gnomad4 FIN exome

AF:

0.00720

Gnomad4 NFE exome

AF:

0.0107

Gnomad4 OTH exome

AF:

0.00814

GnomAD4 genome

AF:

0.00749

AC:

1141

AN:

152324

Hom.:

Cov.:

AF XY:

0.00720

AC XY:

536

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00171

Gnomad4 AMR

AF:

0.00947

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00911

Gnomad4 FIN

AF:

0.00452

Gnomad4 NFE

AF:

0.0113

Gnomad4 OTH

AF:

0.00947

Alfa

AF:

0.0102

Hom.:

Bravo

AF:

0.00716

EpiCase

AF:

0.0109

EpiControl

AF:

0.0112

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

Aug 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

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