rs8103851

Variant names:

• chr19-53894400-C-G
• rs8103851
• NM_002739.5:c.939+1009C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002739.5(PRKCG):​c.939+1009C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 151,864 control chromosomes in the GnomAD database, including 14,805 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 0.44 (14805 hom., cov: 32)
• Consequence: PRKCG NM_002739.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.916
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia type 14

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCG	NM_002739.5	c.939+1009C>G		intron_variant	Intron 9 of 17	ENST00000263431.4	NP_002730.1
PRKCG	NM_001316329.2	c.939+1009C>G		intron_variant	Intron 9 of 18		NP_001303258.1
PRKCG	XM_047439092.1	c.555+1009C>G		intron_variant	Intron 10 of 19		XP_047295048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCG	ENST00000263431.4	c.939+1009C>G		intron_variant	Intron 9 of 17	1	NM_002739.5	ENSP00000263431.3

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66665 AN: 151746 Hom.: 14781 Cov.: 32

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.439 AC: 66732 AN: 151864 Hom.: 14805 Cov.: 32 AF XY: 0.444 AC XY: 32942 AN XY: 74208

African (AFR) AF: 0.488 AC: 20201 AN: 41398

American (AMR) AF: 0.453 AC: 6911 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1493 AN: 3470

East Asian (EAS) AF: 0.416 AC: 2140 AN: 5148

South Asian (SAS) AF: 0.540 AC: 2595 AN: 4804

European-Finnish (FIN) AF: 0.454 AC: 4788 AN: 10542

Middle Eastern (MID) AF: 0.445 AC: 130 AN: 292

European-Non Finnish (NFE) AF: 0.400 AC: 27148 AN: 67940

Other (OTH) AF: 0.435 AC: 916 AN: 2106

Alfa AF: 0.420 Hom.: 1696

Bravo AF: 0.438

Asia WGS AF: 0.509 AC: 1771 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	1.8
DANN	Benign	0.51
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8103851; hg19: chr19-54397654;