Variant chr19-53882183-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000474397.5(PRKCG):c.-323+343A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.972 in 384,370 control chromosomes in the GnomAD database, including 181,592 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.97 ( 72269 hom., cov: 31)

Exomes 𝑓: 0.97 ( 109323 hom. )

Consequence

PRKCG
ENST00000474397.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.105

Variant links:

Genes affected

PRKCG (HGNC:9402): (protein kinase C gamma) Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and 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 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 distinct roles in cells. The protein encoded by this gene is one of the PKC family members. This protein kinase is expressed solely in the brain and spinal cord and its localization is restricted to neurons. It has been demonstrated that several neuronal functions, including long term potentiation (LTP) and long term depression (LTD), specifically require this kinase. Knockout studies in mice also suggest that this kinase may be involved in neuropathic pain development. Defects in this protein have been associated with neurodegenerative disorder spinocerebellar ataxia-14 (SCA14). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

PRKCG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 19-53882183-A-C is Benign according to our data. Variant chr19-53882183-A-C is described in ClinVar as [Benign]. Clinvar id is 1260463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
PRKCG	XM_047439092.1 linkuse as main transcript	c.-323+343A>C	intron_variant
PRKCG	NM_002739.5 linkuse as main transcript		upstream_gene_variant	ENST00000263431.4
PRKCG	NM_001316329.2 linkuse as main transcript		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCG	ENST00000263431.4 linkuse as main transcript			upstream_gene_variant		1	NM_002739.5	P1	P05129-1

Frequencies

GnomAD3 genomes

AF:

0.974

AC:

148173

AN:

152084

Hom.:

72211

Cov.:

show subpopulations

Gnomad AFR

AF:

0.993

Gnomad AMI

AF:

0.893

Gnomad AMR

AF:

0.976

Gnomad ASJ

AF:

0.990

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.995

Gnomad FIN

AF:

0.964

Gnomad MID

AF:

0.984

Gnomad NFE

AF:

0.961

Gnomad OTH

AF:

0.970

GnomAD3 exomes

AF:

0.967

AC:

12212

AN:

12626

Hom.:

5905

AF XY:

0.968

AC XY:

7170

AN XY:

7410

show subpopulations

Gnomad AFR exome

AF:

0.985

Gnomad AMR exome

AF:

0.976

Gnomad ASJ exome

AF:

0.972

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.992

Gnomad FIN exome

AF:

0.962

Gnomad NFE exome

AF:

0.951

Gnomad OTH exome

AF:

0.977

GnomAD4 exome

AF:

0.970

AC:

225275

AN:

232170

Hom.:

109323

Cov.:

AF XY:

0.973

AC XY:

123965

AN XY:

127414

show subpopulations

Gnomad4 AFR exome

AF:

0.993

Gnomad4 AMR exome

AF:

0.978

Gnomad4 ASJ exome

AF:

0.986

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.993

Gnomad4 FIN exome

AF:

0.962

Gnomad4 NFE exome

AF:

0.961

Gnomad4 OTH exome

AF:

0.972

GnomAD4 genome

AF:

0.974

AC:

148289

AN:

152200

Hom.:

72269

Cov.:

AF XY:

0.974

AC XY:

72501

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.993

Gnomad4 AMR

AF:

0.976

Gnomad4 ASJ

AF:

0.990

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.995

Gnomad4 FIN

AF:

0.964

Gnomad4 NFE

AF:

0.961

Gnomad4 OTH

AF:

0.970

Alfa

AF:

0.947

Hom.:

3166

Bravo

AF:

0.976

Asia WGS

AF:

0.996

AC:

3463

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	Sep 25, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.47

Splicing

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