Variant rs2230500 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006255.5(PRKCH):c.1120G>A(p.Val374Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 1,614,004 control chromosomes in the GnomAD database, including 1,583 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.019 ( 190 hom., cov: 32)

Exomes 𝑓: 0.018 ( 1393 hom. )

Consequence

PRKCH
NM_006255.5 missense

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: 2.13

Variant links:

Genes affected

PRKCH (HGNC:9403): (protein kinase C eta) Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role in cells. The protein encoded by this gene is one of the PKC family members. It is a calcium-independent and phospholipids-dependent protein kinase. It is predominantly expressed in epithelial tissues and has been shown to reside specifically in the cell nucleus. This protein kinase can regulate keratinocyte differentiation by activating the MAP kinase MAPK13 (p38delta)-activated protein kinase cascade that targets CCAAT/enhancer-binding protein alpha (CEBPA). It is also found to mediate the transcription activation of the transglutaminase 1 (TGM1) gene. Mutations in this gene are associated with susceptibility to cerebral infarction. [provided by RefSeq, Sep 2015]

PRKCH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019232929).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCH	NM_006255.5 linkuse as main transcript	c.1120G>A	p.Val374Ile	missense_variant	9/14	ENST00000332981.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCH	ENST00000332981.11 linkuse as main transcript	c.1120G>A	p.Val374Ile	missense_variant	9/14	1	NM_006255.5	P1	P24723-1

Frequencies

GnomAD3 genomes

AF:

0.0187

AC:

2851

AN:

152116

Hom.:

188

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00234

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00923

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.258

Gnomad SAS

AF:

0.0228

Gnomad FIN

AF:

0.0327

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0109

Gnomad OTH

AF:

0.0201

GnomAD3 exomes

AF:

0.0308

AC:

7738

AN:

251296

Hom.:

678

AF XY:

0.0299

AC XY:

4064

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.00613

Gnomad ASJ exome

AF:

0.0101

Gnomad EAS exome

AF:

0.268

Gnomad SAS exome

AF:

0.0123

Gnomad FIN exome

AF:

0.0357

Gnomad NFE exome

AF:

0.0106

Gnomad OTH exome

AF:

0.0181

GnomAD4 exome

AF:

0.0180

AC:

26311

AN:

1461768

Hom.:

1393

Cov.:

AF XY:

0.0177

AC XY:

12888

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.00167

Gnomad4 AMR exome

AF:

0.00653

Gnomad4 ASJ exome

AF:

0.00911

Gnomad4 EAS exome

AF:

0.242

Gnomad4 SAS exome

AF:

0.0128

Gnomad4 FIN exome

AF:

0.0322

Gnomad4 NFE exome

AF:

0.0105

Gnomad4 OTH exome

AF:

0.0258

GnomAD4 genome

AF:

0.0187

AC:

2854

AN:

152236

Hom.:

190

Cov.:

AF XY:

0.0211

AC XY:

1568

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.00233

Gnomad4 AMR

AF:

0.00922

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.258

Gnomad4 SAS

AF:

0.0228

Gnomad4 FIN

AF:

0.0327

Gnomad4 NFE

AF:

0.0109

Gnomad4 OTH

AF:

0.0241

Alfa

AF:

0.0186

Hom.:

279

Bravo

AF:

0.0170

TwinsUK

AF:

0.0119

AC:

ALSPAC

AF:

0.0101

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00837

AC:

ExAC

AF:

0.0294

AC:

3570

Asia WGS

AF:

0.135

AC:

468

AN:

3478

EpiCase

AF:

0.00960

EpiControl

AF:

0.00865

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Cerebral infarction, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Feb 01, 2007

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.079

T;.;.

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.55

T;T;T

MetaRNN

Benign

0.0019

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.47

N;.;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Uncertain

0.71

PROVEAN

Benign

0.22

N;N;N

REVEL

Benign

0.064

Sift

Benign

0.30

T;T;T

Sift4G

Benign

0.41

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.056

MPC

0.41

ClinPred

0.0051

GERP RS

4.6

Varity_R

0.062

gMVP

0.14

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