rs2242245

chr19-53900547-T-C

Variant summary

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

The NM_002739.5(PRKCG):c.1437-64T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 1,614,186 control chromosomes in the GnomAD database, including 997 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (193 hom., cov: 32)
  • Exomes 𝑓: 0.015 (804 hom.)
• Consequence: PRKCG NM_002739.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.34

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=-0.98).
• BP6: Variant 19-53900547-T-C is Benign according to our data. Variant chr19-53900547-T-C is described in ClinVar as [Benign]. Clinvar id is 1270032.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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	UniProt
PRKCG	NM_002739.5	c.1437-64T>C		intron_variant		ENST00000263431.4
PRKCG	NM_001316329.2	c.1437-64T>C		intron_variant
PRKCG	XM_047439092.1	c.1053-64T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCG	ENST00000263431.4	c.1437-64T>C		intron_variant		1	NM_002739.5	P1

Frequencies

GnomAD3 genomes AF: 0.0331 AC: 5041 AN: 152204 Hom.: 193 Cov.: 32

Gnomad AFR AF: 0.0786

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0264

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0513

Gnomad FIN AF: 0.00282

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00550

Gnomad OTH AF: 0.0330

GnomAD4 exome AF: 0.0151 AC: 22077 AN: 1461864 Hom.: 804 Cov.: 33 AF XY: 0.0153 AC XY: 11126 AN XY: 727238

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: 0.00382

Gnomad4 NFE exome AF: 0.00533

Gnomad4 OTH exome AF: 0.0218

GnomAD4 genome AF: 0.0332 AC: 5051 AN: 152322 Hom.: 193 Cov.: 32 AF XY: 0.0338 AC XY: 2521 AN XY: 74488

Gnomad4 AFR AF: 0.0787

Gnomad4 AMR AF: 0.0264

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.0503

Gnomad4 FIN AF: 0.00282

Gnomad4 NFE AF: 0.00550

Gnomad4 OTH AF: 0.0326

Alfa AF: 0.0140 Hom.: 58

Bravo AF: 0.0375

Asia WGS AF: 0.104 AC: 360 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

May 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.0050
Dann	Benign	0.29

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

Other links and lift over

dbSNP: rs2242245; hg19: chr19-54403801; COSMIC: COSV54725610;