rs454006

chr19-53886867-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002739.5(PRKCG):c.285+2624T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 152,146 control chromosomes in the GnomAD database, including 11,108 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (11108 hom., cov: 32)
• Consequence: PRKCG NM_002739.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.138

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCG	NM_002739.5	c.285+2624T>C		intron_variant		ENST00000263431.4
PRKCG	NM_001316329.2	c.285+2624T>C		intron_variant
PRKCG	XM_047439092.1	c.-100+2624T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCG	ENST00000263431.4	c.285+2624T>C		intron_variant		1	NM_002739.5	P1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54681 AN: 152028 Hom.: 11071 Cov.: 32

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.376

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.360 AC: 54770 AN: 152146 Hom.: 11108 Cov.: 32 AF XY: 0.357 AC XY: 26558 AN XY: 74368

Gnomad4 AFR AF: 0.558

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.380

Alfa AF: 0.289 Hom.: 13455

Bravo AF: 0.377

Asia WGS AF: 0.374 AC: 1299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	4.4
Dann	Benign	0.44

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: rs454006; hg19: chr19-54390121;