Variant rs2230501 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_006255.5(PRKCH):c.1122A>C(p.Val374=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 1,614,038 control chromosomes in the GnomAD database, including 1,583 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.019 ( 190 hom., cov: 32)

Exomes 𝑓: 0.018 ( 1393 hom. )

Consequence

PRKCH
NM_006255.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00400

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP7

Synonymous conserved (PhyloP=-0.004 with no splicing effect.

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.1122A>C	p.Val374=	synonymous_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.1122A>C	p.Val374=	synonymous_variant	9/14	1	NM_006255.5	P1	P24723-1

Frequencies

GnomAD3 genomes

AF:

0.0187

AC:

2852

AN:

152146

Hom.:

188

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00234

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00929

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.258

Gnomad SAS

AF:

0.0227

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:

7739

AN:

251304

Hom.:

678

AF XY:

0.0299

AC XY:

4064

AN XY:

135808

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:

1461772

Hom.:

1393

Cov.:

AF XY:

0.0177

AC XY:

12889

AN XY:

727188

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:

0.0188

AC:

2855

AN:

152266

Hom.:

190

Cov.:

AF XY:

0.0211

AC XY:

1569

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00233

Gnomad4 AMR

AF:

0.00928

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.258

Gnomad4 SAS

AF:

0.0227

Gnomad4 FIN

AF:

0.0327

Gnomad4 NFE

AF:

0.0109

Gnomad4 OTH

AF:

0.0242

Alfa

AF:

0.00831

Hom.:

Bravo

AF:

0.0170

Asia WGS

AF:

0.135

AC:

468

AN:

3478

EpiCase

AF:

0.00960

EpiControl

AF:

0.00865

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

5.1

DANN

Benign

0.69

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over