rs454006

Variant names:

• chr19-53886867-T-C
• rs454006
• NM_002739.5:c.285+2624T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002739.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCG	NM_002739.5	MANE Select	c.285+2624T>C		intron	N/A	NP_002730.1	P05129-1
	PRKCG	NM_001316329.2		c.285+2624T>C		intron	N/A	NP_001303258.1	A0A804HIU5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCG	ENST00000263431.4	TSL:1 MANE Select	c.285+2624T>C		intron	N/A	ENSP00000263431.3	P05129-1
	PRKCG	ENST00000682028.1		c.285+2624T>C		intron	N/A	ENSP00000507230.1	A0A804HIU5
	PRKCG	ENST00000683513.1		c.285+2624T>C		intron	N/A	ENSP00000506809.1	A0A804HHY0

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

African (AFR) AF: 0.558 AC: 23161 AN: 41494

American (AMR) AF: 0.354 AC: 5416 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1221 AN: 3472

East Asian (EAS) AF: 0.312 AC: 1618 AN: 5180

South Asian (SAS) AF: 0.366 AC: 1764 AN: 4818

European-Finnish (FIN) AF: 0.220 AC: 2326 AN: 10594

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18057 AN: 67992

Other (OTH) AF: 0.380 AC: 803 AN: 2112

Alfa AF: 0.297 Hom.: 31256

Bravo AF: 0.377

Asia WGS AF: 0.374 AC: 1299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.4
DANN	Benign	0.44
PhyloP100		0.14
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: rs454006; hg19: chr19-54390121;