rs2242244

Positions:

chr19-53900671-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002739.5(PRKCG):c.1497T>C(p.Phe499Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 1,614,200 control chromosomes in the GnomAD database, including 1,002 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 198 hom., cov: 32)

Exomes 𝑓: 0.015 ( 804 hom. )

Consequence

PRKCG
NM_002739.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.83

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:

PRKCG (HGNC:):

PRKCG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 19-53900671-T-C is Benign according to our data. Variant chr19-53900671-T-C is described in ClinVar as [Benign]. Clinvar id is 194378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-53900671-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.83 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCG	NM_002739.5 linkuse as main transcript	c.1497T>C	p.Phe499Phe	synonymous_variant	14/18	ENST00000263431.4	NP_002730.1	P05129-1
PRKCG	NM_001316329.2 linkuse as main transcript	c.1497T>C	p.Phe499Phe	synonymous_variant	14/19		NP_001303258.1	P05129B7Z3W6B2R5T1A0A804HIU5
PRKCG	XM_047439092.1 linkuse as main transcript	c.1113T>C	p.Phe371Phe	synonymous_variant	15/20		XP_047295048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCG	ENST00000263431.4 linkuse as main transcript	c.1497T>C	p.Phe499Phe	synonymous_variant	14/18	1	NM_002739.5	ENSP00000263431.3		P05129-1

Frequencies

GnomAD3 genomes

AF:

0.0332

AC:

5046

AN:

152192

Hom.:

198

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0788

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0263

Gnomad ASJ

AF:

0.00691

Gnomad EAS

AF:

0.121

Gnomad SAS

AF:

0.0513

Gnomad FIN

AF:

0.00282

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00548

Gnomad OTH

AF:

0.0330

GnomAD3 exomes

AF:

0.0301

AC:

7578

AN:

251482

Hom.:

276

AF XY:

0.0270

AC XY:

3672

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.0807

Gnomad AMR exome

AF:

0.0504

Gnomad ASJ exome

AF:

0.00615

Gnomad EAS exome

AF:

0.119

Gnomad SAS exome

AF:

0.0428

Gnomad FIN exome

AF:

0.00346

Gnomad NFE exome

AF:

0.00640

Gnomad OTH exome

AF:

0.0246

GnomAD4 exome

AF:

0.0151

AC:

22079

AN:

1461890

Hom.:

804

Cov.:

AF XY:

0.0153

AC XY:

11127

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0786

Gnomad4 AMR exome

AF:

0.0465

Gnomad4 ASJ exome

AF:

0.00631

Gnomad4 EAS exome

AF:

0.151

Gnomad4 SAS exome

AF:

0.0419

Gnomad4 FIN exome

AF:

0.00384

Gnomad4 NFE exome

AF:

0.00533

Gnomad4 OTH exome

AF:

0.0218

GnomAD4 genome

AF:

0.0332

AC:

5056

AN:

152310

Hom.:

198

Cov.:

AF XY:

0.0338

AC XY:

2520

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0789

Gnomad4 AMR

AF:

0.0264

Gnomad4 ASJ

AF:

0.00691

Gnomad4 EAS

AF:

0.121

Gnomad4 SAS

AF:

0.0503

Gnomad4 FIN

AF:

0.00282

Gnomad4 NFE

AF:

0.00548

Gnomad4 OTH

AF:

0.0327

Alfa

AF:

0.0130

Hom.:

Bravo

AF:

0.0376

Asia WGS

AF:

0.104

AC:

359

AN:

3478

EpiCase

AF:

0.00605

EpiControl

AF:

0.00616

ClinVar

Significance: Benign

Submissions summary: Benign:4

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	May 05, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Nov 08, 2014

- -

Spinocerebellar ataxia type 14

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.98

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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