Variant chr17-66688960-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002737.3(PRKCA):c.831G>A(p.Leu277=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 1,590,964 control chromosomes in the GnomAD database, including 95,976 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6907 hom., cov: 32)

Exomes 𝑓: 0.35 ( 89069 hom. )

Consequence

PRKCA
NM_002737.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.69

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 17-66688960-G-A is Benign according to our data. Variant chr17-66688960-G-A is described in ClinVar as [Benign]. Clinvar id is 1295165.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.69 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.355 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.831G>A	p.Leu277=	synonymous_variant	8/17	ENST00000413366.8	NP_002728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
PRKCA	ENST00000413366.8 linkuse as main transcript	c.831G>A	p.Leu277=	synonymous_variant	8/17	1	NM_002737.3	ENSP00000408695	P1
PRKCA	ENST00000578063.5 linkuse as main transcript	c.831G>A	p.Leu277=	synonymous_variant, NMD_transcript_variant	8/10	1		ENSP00000462087
PRKCA	ENST00000284384.6 linkuse as main transcript	c.*433G>A		3_prime_UTR_variant, NMD_transcript_variant	9/15	5		ENSP00000284384

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42653

AN:

151822

Hom.:

6904

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.417

Gnomad AMR

AF:

0.299

Gnomad ASJ

AF:

0.416

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.339

Gnomad FIN

AF:

0.382

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.358

Gnomad OTH

AF:

0.293

GnomAD3 exomes

AF:

0.316

AC:

77590

AN:

245280

Hom.:

13382

AF XY:

0.325

AC XY:

43058

AN XY:

132494

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.298

Gnomad ASJ exome

AF:

0.420

Gnomad EAS exome

AF:

0.108

Gnomad SAS exome

AF:

0.352

Gnomad FIN exome

AF:

0.366

Gnomad NFE exome

AF:

0.355

Gnomad OTH exome

AF:

0.335

GnomAD4 exome

AF:

0.345

AC:

497127

AN:

1439026

Hom.:

89069

Cov.:

AF XY:

0.346

AC XY:

248210

AN XY:

716542

show subpopulations

Gnomad4 AFR exome

AF:

0.107

Gnomad4 AMR exome

AF:

0.300

Gnomad4 ASJ exome

AF:

0.420

Gnomad4 EAS exome

AF:

0.131

Gnomad4 SAS exome

AF:

0.354

Gnomad4 FIN exome

AF:

0.367

Gnomad4 NFE exome

AF:

0.359

Gnomad4 OTH exome

AF:

0.335

GnomAD4 genome

AF:

0.281

AC:

42661

AN:

151938

Hom.:

6907

Cov.:

AF XY:

0.283

AC XY:

21003

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.119

Gnomad4 AMR

AF:

0.299

Gnomad4 ASJ

AF:

0.416

Gnomad4 EAS

AF:

0.111

Gnomad4 SAS

AF:

0.340

Gnomad4 FIN

AF:

0.382

Gnomad4 NFE

AF:

0.358

Gnomad4 OTH

AF:

0.296

Alfa

AF:

0.330

Hom.:

4912

Bravo

AF:

0.266

Asia WGS

AF:

0.240

AC:

836

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 17, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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