chr19-53882566-C-T

Position:

chr19-53882566-C-T

Variant summary

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

The NM_002739.5(PRKCG):c.72C>T(p.Ala24=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.95 in 1,614,066 control chromosomes in the GnomAD database, including 730,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.90 ( 62102 hom., cov: 31)

Exomes 𝑓: 0.96 ( 668192 hom. )

Consequence

PRKCG
NM_002739.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -1.16

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 19-53882566-C-T is Benign according to our data. Variant chr19-53882566-C-T is described in ClinVar as [Benign]. Clinvar id is 130037.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-53882566-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.16 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PRKCG	NM_002739.5 linkuse as main transcript	c.72C>T	p.Ala24=	synonymous_variant	1/18	ENST00000263431.4
PRKCG	NM_001316329.2 linkuse as main transcript	c.72C>T	p.Ala24=	synonymous_variant	1/19
PRKCG	XM_047439092.1 linkuse as main transcript	c.-313C>T		5_prime_UTR_variant	2/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCG	ENST00000263431.4 linkuse as main transcript	c.72C>T	p.Ala24=	synonymous_variant	1/18	1	NM_002739.5	P1	P05129-1

Frequencies

GnomAD3 genomes

AF:

0.898

AC:

136490

AN:

152074

Hom.:

62072

Cov.:

show subpopulations

Gnomad AFR

AF:

0.738

Gnomad AMI

AF:

0.978

Gnomad AMR

AF:

0.942

Gnomad ASJ

AF:

0.946

Gnomad EAS

AF:

0.989

Gnomad SAS

AF:

0.993

Gnomad FIN

AF:

0.963

Gnomad MID

AF:

0.924

Gnomad NFE

AF:

0.957

Gnomad OTH

AF:

0.899

GnomAD3 exomes

AF:

0.950

AC:

238694

AN:

251208

Hom.:

113857

AF XY:

0.955

AC XY:

129836

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.729

Gnomad AMR exome

AF:

0.964

Gnomad ASJ exome

AF:

0.943

Gnomad EAS exome

AF:

0.989

Gnomad SAS exome

AF:

0.992

Gnomad FIN exome

AF:

0.965

Gnomad NFE exome

AF:

0.958

Gnomad OTH exome

AF:

0.951

GnomAD4 exome

AF:

0.955

AC:

1396639

AN:

1461874

Hom.:

668192

Cov.:

AF XY:

0.957

AC XY:

696104

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.731

Gnomad4 AMR exome

AF:

0.960

Gnomad4 ASJ exome

AF:

0.944

Gnomad4 EAS exome

AF:

0.994

Gnomad4 SAS exome

AF:

0.991

Gnomad4 FIN exome

AF:

0.963

Gnomad4 NFE exome

AF:

0.958

Gnomad4 OTH exome

AF:

0.947

GnomAD4 genome

AF:

0.897

AC:

136579

AN:

152192

Hom.:

62102

Cov.:

AF XY:

0.900

AC XY:

66964

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.738

Gnomad4 AMR

AF:

0.943

Gnomad4 ASJ

AF:

0.946

Gnomad4 EAS

AF:

0.989

Gnomad4 SAS

AF:

0.994

Gnomad4 FIN

AF:

0.963

Gnomad4 NFE

AF:

0.957

Gnomad4 OTH

AF:

0.900

Alfa

AF:

0.933

Hom.:

36891

Bravo

AF:

0.888

Asia WGS

AF:

0.962

AC:

3345

AN:

3478

EpiCase

AF:

0.961

EpiControl

AF:

0.962

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Spinocerebellar ataxia type 14

Benign:5

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Oct 25, 2021	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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. -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 10, 2014	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 15, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 25, 2019	- -

not specified

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 29, 2016	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.92

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