Variant 17-66688447-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000413366.8(PRKCA):c.821+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,613,594 control chromosomes in the GnomAD database, including 15,375 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 0.12 ( 1175 hom., cov: 32)

Exomes 𝑓: 0.14 ( 14200 hom. )

Consequence

PRKCA
ENST00000413366.8 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0720

Variant links:

Genes affected

PRKCA (HGNC:9393): (protein kinase C alpha) 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. This kinase has been reported to play roles in many different cellular processes, such as cell adhesion, cell transformation, cell cycle checkpoint, and cell volume control. Knockout studies in mice suggest that this kinase may be a fundamental regulator of cardiac contractility and Ca(2+) handling in myocytes. [provided by RefSeq, Jul 2008]

PRKCA 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 (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCA	NM_002737.3 linkuse as main transcript	c.821+11C>T		intron_variant		ENST00000413366.8	NP_002728.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
PRKCA	ENST00000413366.8 linkuse as main transcript	c.821+11C>T	intron_variant	1	NM_002737.3	ENSP00000408695	P1
PRKCA	ENST00000578063.5 linkuse as main transcript	c.821+11C>T	intron_variant, NMD_transcript_variant	1		ENSP00000462087
PRKCA	ENST00000284384.6 linkuse as main transcript	c.*423+11C>T	intron_variant, NMD_transcript_variant	5		ENSP00000284384

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18039

AN:

151958

Hom.:

1178

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0705

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.172

Gnomad EAS

AF:

0.0549

Gnomad SAS

AF:

0.177

Gnomad FIN

AF:

0.159

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.130

GnomAD3 exomes

AF:

0.138

AC:

34643

AN:

251120

Hom.:

2724

AF XY:

0.142

AC XY:

19289

AN XY:

135734

show subpopulations

Gnomad AFR exome

AF:

0.0685

Gnomad AMR exome

AF:

0.151

Gnomad ASJ exome

AF:

0.177

Gnomad EAS exome

AF:

0.0606

Gnomad SAS exome

AF:

0.182

Gnomad FIN exome

AF:

0.157

Gnomad NFE exome

AF:

0.137

Gnomad OTH exome

AF:

0.140

GnomAD4 exome

AF:

0.135

AC:

197890

AN:

1461518

Hom.:

14200

Cov.:

AF XY:

0.137

AC XY:

99551

AN XY:

727070

show subpopulations

Gnomad4 AFR exome

AF:

0.0677

Gnomad4 AMR exome

AF:

0.151

Gnomad4 ASJ exome

AF:

0.178

Gnomad4 EAS exome

AF:

0.0548

Gnomad4 SAS exome

AF:

0.185

Gnomad4 FIN exome

AF:

0.153

Gnomad4 NFE exome

AF:

0.134

Gnomad4 OTH exome

AF:

0.133

GnomAD4 genome

AF:

0.119

AC:

18041

AN:

152076

Hom.:

1175

Cov.:

AF XY:

0.122

AC XY:

9065

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0703

Gnomad4 AMR

AF:

0.136

Gnomad4 ASJ

AF:

0.172

Gnomad4 EAS

AF:

0.0547

Gnomad4 SAS

AF:

0.178

Gnomad4 FIN

AF:

0.159

Gnomad4 NFE

AF:

0.136

Gnomad4 OTH

AF:

0.130

Alfa

AF:

0.134

Hom.:

2199

Bravo

AF:

0.114

Asia WGS

AF:

0.128

AC:

445

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.4

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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