19-53884243-C-T

Position:

chr19-53884243-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.285C>T(p.Asp95Asp) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00741 in 1,613,684 control chromosomes in the GnomAD database, including 467 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 230 hom., cov: 32)

Exomes 𝑓: 0.0049 ( 237 hom. )

Consequence

PRKCG
NM_002739.5 splice_region, synonymous

Scores

Splicing: ADA: 0.004953

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.272

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 19-53884243-C-T is Benign according to our data. Variant chr19-53884243-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 330058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-53884243-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.272 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0974 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.285C>T	p.Asp95Asp	splice_region_variant, synonymous_variant	3/18	ENST00000263431.4	NP_002730.1	P05129-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCG	ENST00000263431.4 linkuse as main transcript	c.285C>T	p.Asp95Asp	splice_region_variant, synonymous_variant	3/18	1	NM_002739.5	ENSP00000263431.3		P05129-1

Frequencies

GnomAD3 genomes

AF:

0.0311

AC:

4737

AN:

152128

Hom.:

229

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0998

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.0167

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.0106

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.00215

Gnomad OTH

AF:

0.0344

GnomAD3 exomes

AF:

0.0115

AC:

2887

AN:

251378

Hom.:

117

AF XY:

0.00918

AC XY:

1247

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.106

Gnomad AMR exome

AF:

0.0128

Gnomad ASJ exome

AF:

0.0109

Gnomad EAS exome

AF:

0.0109

Gnomad SAS exome

AF:

0.00176

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00239

Gnomad OTH exome

AF:

0.0147

GnomAD4 exome

AF:

0.00493

AC:

7208

AN:

1461438

Hom.:

237

Cov.:

AF XY:

0.00457

AC XY:

3323

AN XY:

727012

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.0144

Gnomad4 ASJ exome

AF:

0.0117

Gnomad4 EAS exome

AF:

0.00564

Gnomad4 SAS exome

AF:

0.00175

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.00136

Gnomad4 OTH exome

AF:

0.0118

GnomAD4 genome

AF:

0.0312

AC:

4755

AN:

152246

Hom.:

230

Cov.:

AF XY:

0.0305

AC XY:

2267

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.100

Gnomad4 AMR

AF:

0.0167

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.0106

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00215

Gnomad4 OTH

AF:

0.0341

Alfa

AF:

0.00785

Hom.:

Bravo

AF:

0.0358

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.00311

EpiControl

AF:

0.00338

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 10, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Spinocerebellar ataxia type 14

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
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	Apr 05, 2016	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Apr 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.99

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0050

dbscSNV1_RF

Benign

0.14

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