19-53891711-T-C

Position:

chr19-53891711-T-C

Variant summary

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

The ENST00000263431.4(PRKCG):c.567T>C(p.Asn189Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 1,613,570 control chromosomes in the GnomAD database, including 135,641 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10658 hom., cov: 31)

Exomes 𝑓: 0.41 ( 124983 hom. )

Consequence

PRKCG
ENST00000263431.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.335

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=-0.53).

BP6

Variant 19-53891711-T-C is Benign according to our data. Variant chr19-53891711-T-C is described in ClinVar as [Benign]. Clinvar id is 130036.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-53891711-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.335 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.419 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.567T>C	p.Asn189Asn	synonymous_variant	6/18	ENST00000263431.4	NP_002730.1	P05129-1
PRKCG	NM_001316329.2 linkuse as main transcript	c.567T>C	p.Asn189Asn	synonymous_variant	6/19		NP_001303258.1	P05129B7Z3W6B2R5T1A0A804HIU5
PRKCG	XM_047439092.1 linkuse as main transcript	c.183T>C	p.Asn61Asn	synonymous_variant	7/20		XP_047295048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCG	ENST00000263431.4 linkuse as main transcript	c.567T>C	p.Asn189Asn	synonymous_variant	6/18	1	NM_002739.5	ENSP00000263431.3		P05129-1

Frequencies

GnomAD3 genomes

AF:

0.362

AC:

54960

AN:

151852

Hom.:

10655

Cov.:

show subpopulations

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.500

Gnomad AMR

AF:

0.427

Gnomad ASJ

AF:

0.445

Gnomad EAS

AF:

0.301

Gnomad SAS

AF:

0.422

Gnomad FIN

AF:

0.458

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.416

Gnomad OTH

AF:

0.373

GnomAD3 exomes

AF:

0.406

AC:

102157

AN:

251486

Hom.:

21248

AF XY:

0.409

AC XY:

55575

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.217

Gnomad AMR exome

AF:

0.470

Gnomad ASJ exome

AF:

0.438

Gnomad EAS exome

AF:

0.300

Gnomad SAS exome

AF:

0.433

Gnomad FIN exome

AF:

0.454

Gnomad NFE exome

AF:

0.412

Gnomad OTH exome

AF:

0.403

GnomAD4 exome

AF:

0.411

AC:

600911

AN:

1461600

Hom.:

124983

Cov.:

AF XY:

0.412

AC XY:

299808

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.210

Gnomad4 AMR exome

AF:

0.463

Gnomad4 ASJ exome

AF:

0.438

Gnomad4 EAS exome

AF:

0.289

Gnomad4 SAS exome

AF:

0.432

Gnomad4 FIN exome

AF:

0.448

Gnomad4 NFE exome

AF:

0.416

Gnomad4 OTH exome

AF:

0.402

GnomAD4 genome

AF:

0.362

AC:

54976

AN:

151970

Hom.:

10658

Cov.:

AF XY:

0.365

AC XY:

27074

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.214

Gnomad4 AMR

AF:

0.427

Gnomad4 ASJ

AF:

0.445

Gnomad4 EAS

AF:

0.300

Gnomad4 SAS

AF:

0.422

Gnomad4 FIN

AF:

0.458

Gnomad4 NFE

AF:

0.416

Gnomad4 OTH

AF:

0.376

Alfa

AF:

0.385

Hom.:

6983

Bravo

AF:

0.352

Asia WGS

AF:

0.359

AC:

1251

AN:

3478

EpiCase

AF:

0.420

EpiControl

AF:

0.411

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Spinocerebellar ataxia type 14

Benign:4

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

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 12, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 25, 2019	- -

not specified

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

4.4

DANN

Benign

0.49

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