Variant 8-143866163-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_031308.4(EPPK1):c.7091G>A(p.Arg2364Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0043 ( 0 hom., cov: 2)

Exomes 𝑓: 0.0021 ( 9 hom. )

Failed GnomAD Quality Control

Consequence

EPPK1
NM_031308.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.309

Variant links:

Genes affected

EPPK1 (HGNC:15577): (epiplakin 1) The protein encoded by this gene belongs to the plakin family of proteins, which play a role in the organization of cytoskeletal architecture. This family member is composed of several highly homologous plakin repeats. It may function to maintain the integrity of keratin intermediate filament networks in epithelial cells. Studies of the orthologous mouse protein suggest that it accelerates keratinocyte migration during wound healing. [provided by RefSeq, Oct 2013]

EPPK1 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=0.027334511).

BP6

Variant 8-143866163-C-T is Benign according to our data. Variant chr8-143866163-C-T is described in ClinVar as [Benign]. Clinvar id is 3034991.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00206 (828/401314) while in subpopulation AFR AF= 0.0286 (318/11118). AF 95% confidence interval is 0.026. There are 9 homozygotes in gnomad4_exome. There are 406 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPPK1	NM_031308.4 linkuse as main transcript	c.7091G>A	p.Arg2364Gln	missense_variant	2/2	ENST00000615648.2	NP_112598.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPPK1	ENST00000615648.2 linkuse as main transcript	c.7091G>A	p.Arg2364Gln	missense_variant	2/2	5	NM_031308.4	ENSP00000484472	A2
EPPK1	ENST00000568225.2 linkuse as main transcript	c.7016G>A	p.Arg2339Gln	missense_variant	1/1			ENSP00000456124	P4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

2526

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00413

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000978

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0104

AC:

2054

AN:

198012

Hom.:

AF XY:

0.00924

AC XY:

1002

AN XY:

108466

show subpopulations

Gnomad AFR exome

AF:

0.0562

Gnomad AMR exome

AF:

0.00854

Gnomad ASJ exome

AF:

0.00646

Gnomad EAS exome

AF:

0.0374

Gnomad SAS exome

AF:

0.00514

Gnomad FIN exome

AF:

0.00628

Gnomad NFE exome

AF:

0.00564

Gnomad OTH exome

AF:

0.0102

GnomAD4 exome

AF:

0.00206

AC:

828

AN:

401314

Hom.:

Cov.:

AF XY:

0.00192

AC XY:

406

AN XY:

211136

show subpopulations

Gnomad4 AFR exome

AF:

0.0286

Gnomad4 AMR exome

AF:

0.00384

Gnomad4 ASJ exome

AF:

0.000967

Gnomad4 EAS exome

AF:

0.00300

Gnomad4 SAS exome

AF:

0.00121

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.000910

Gnomad4 OTH exome

AF:

0.00322

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00431

AC:

AN:

2550

Hom.:

Cov.:

AF XY:

0.00508

AC XY:

AN XY:

1182

show subpopulations

Gnomad4 AFR

AF:

0.0163

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00413

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000982

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00388

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.0000331

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

EPPK1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 15, 2021

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.034

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.0042

MetaRNN

Benign

0.027

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.20

Sift4G

Benign

0.88

T;T

Vest4

0.031

MVP

0.14

ClinPred

0.018

GERP RS

0.91

Varity_R

0.014

gMVP

0.58

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