19-53882183-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.105

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCG	XM_047439092.1	c.-323+343A>C		intron_variant
PRKCG	NM_002739.5			upstream_gene_variant		ENST00000263431.4
PRKCG	NM_001316329.2			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCG	ENST00000263431.4			upstream_gene_variant		1	NM_002739.5	P1

Frequencies

GnomAD3 genomes AF: 0.974 AC: 148173 AN: 152084 Hom.: 72211 Cov.: 31

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

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.: 2 AF XY: 0.973 AC XY: 123965 AN XY: 127414

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.: 31 AF XY: 0.974 AC XY: 72501 AN XY: 74404

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	14
Dann	Benign	0.47

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs307942; hg19: chr19-54385437;