chr19-53888383-T-C

Variant names:

• chr19-53888383-T-C
• rs402691
• NM_002739.5:c.286-1255T>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.286-1255T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 151,784 control chromosomes in the GnomAD database, including 13,342 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 0.39 (13342 hom., cov: 32)
• Consequence: PRKCG NM_002739.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 2 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCG	NM_002739.5	c.286-1255T>C		intron_variant	Intron 3 of 17	ENST00000263431.4	NP_002730.1
PRKCG	NM_001316329.2	c.286-1255T>C		intron_variant	Intron 3 of 18		NP_001303258.1
PRKCG	XM_047439092.1	c.-99-1255T>C		intron_variant	Intron 4 of 19		XP_047295048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCG	ENST00000263431.4	c.286-1255T>C		intron_variant	Intron 3 of 17	1	NM_002739.5	ENSP00000263431.3

Frequencies

GnomAD3 genomes AF: 0.389 AC: 58974 AN: 151666 Hom.: 13298 Cov.: 32

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.389 AC: 59076 AN: 151784 Hom.: 13342 Cov.: 32 AF XY: 0.385 AC XY: 28539 AN XY: 74182

African (AFR) AF: 0.635 AC: 26191 AN: 41264

American (AMR) AF: 0.372 AC: 5667 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1345 AN: 3466

East Asian (EAS) AF: 0.312 AC: 1615 AN: 5180

South Asian (SAS) AF: 0.371 AC: 1787 AN: 4816

European-Finnish (FIN) AF: 0.226 AC: 2382 AN: 10544

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.277 AC: 18800 AN: 67948

Other (OTH) AF: 0.411 AC: 868 AN: 2110

Alfa AF: 0.327 Hom.: 1247

Bravo AF: 0.412

Asia WGS AF: 0.381 AC: 1325 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	0.083
DANN	Benign	0.28
PhyloP100		-1.4
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: rs402691; hg19: chr19-54391637;