Variant 17-66302841-T-TG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_002737.3(PRKCA):c.-4dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,575,856 control chromosomes in the GnomAD database, including 11,361 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.12 ( 1248 hom., cov: 30)

Exomes 𝑓: 0.11 ( 10113 hom. )

Consequence

PRKCA
NM_002737.3 5_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0800

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 -10 ACMG points.

BP6

Variant 17-66302841-T-TG is Benign according to our data. Variant chr17-66302841-T-TG is described in ClinVar as [Likely_benign]. Clinvar id is 3056232.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCA	NM_002737.3 linkuse as main transcript	c.-4dup		5_prime_UTR_variant	1/17	ENST00000413366.8

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
PRKCA	ENST00000413366.8 linkuse as main transcript	c.-4dup	5_prime_UTR_variant	1/17	1	NM_002737.3	P1
PRKCA	ENST00000578063.5 linkuse as main transcript	c.-4dup	5_prime_UTR_variant, NMD_transcript_variant	1/10	1
PRKCA	ENST00000583361.1 linkuse as main transcript	n.41dup	non_coding_transcript_exon_variant	1/3	3
PRKCA	ENST00000284384.6 linkuse as main transcript		upstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.124

AC:

18675

AN:

151002

Hom.:

1238

Cov.:

show subpopulations

Gnomad AFR

AF:

0.130

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.116

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.162

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.106

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.124

GnomAD3 exomes

AF:

0.131

AC:

27312

AN:

208084

Hom.:

1996

AF XY:

0.136

AC XY:

15430

AN XY:

113442

show subpopulations

Gnomad AFR exome

AF:

0.130

Gnomad AMR exome

AF:

0.119

Gnomad ASJ exome

AF:

0.112

Gnomad EAS exome

AF:

0.149

Gnomad SAS exome

AF:

0.218

Gnomad FIN exome

AF:

0.172

Gnomad NFE exome

AF:

0.100

Gnomad OTH exome

AF:

0.134

GnomAD4 exome

AF:

0.113

AC:

161323

AN:

1424742

Hom.:

10113

Cov.:

AF XY:

0.117

AC XY:

82557

AN XY:

707742

show subpopulations

Gnomad4 AFR exome

AF:

0.129

Gnomad4 AMR exome

AF:

0.117

Gnomad4 ASJ exome

AF:

0.110

Gnomad4 EAS exome

AF:

0.188

Gnomad4 SAS exome

AF:

0.220

Gnomad4 FIN exome

AF:

0.169

Gnomad4 NFE exome

AF:

0.0992

Gnomad4 OTH exome

AF:

0.119

GnomAD4 genome

AF:

0.124

AC:

18707

AN:

151114

Hom.:

1248

Cov.:

AF XY:

0.130

AC XY:

9581

AN XY:

73842

show subpopulations

Gnomad4 AFR

AF:

0.130

Gnomad4 AMR

AF:

0.116

Gnomad4 ASJ

AF:

0.114

Gnomad4 EAS

AF:

0.162

Gnomad4 SAS

AF:

0.225

Gnomad4 FIN

AF:

0.169

Gnomad4 NFE

AF:

0.105

Gnomad4 OTH

AF:

0.131

Bravo

AF:

0.116

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PRKCA-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 22, 2020

This variant is classified as likely 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

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