rs13017044

Variant names:

• chr2-46006210-G-A
• rs13017044
• NM_005400.3:c.1064-1252G>A

Variant summary

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

The NM_005400.3(PRKCE):​c.1064-1252G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,206 control chromosomes in the GnomAD database, including 4,023 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 0.22 (4023 hom., cov: 33)
• Consequence: PRKCE NM_005400.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199
• Publications: 4 publications found

Genes affected

PRKCE (HGNC:9401): (protein kinase C epsilon) Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the 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 family members 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 a distinct role in cells. The protein encoded by this gene is one of the PKC family members. This kinase has been shown to be involved in many different cellular functions, such as neuron channel activation, apoptosis, cardioprotection from ischemia, heat shock response, as well as insulin exocytosis. Knockout studies in mice suggest that this kinase is important for lipopolysaccharide (LPS)-mediated signaling in activated macrophages and may also play a role in controlling anxiety-like behavior. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCE	NM_005400.3	c.1064-1252G>A		intron_variant	Intron 8 of 14	ENST00000306156.8	NP_005391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCE	ENST00000306156.8	c.1064-1252G>A		intron_variant	Intron 8 of 14	1	NM_005400.3	ENSP00000306124.3
PRKCE	ENST00000394874.1	c.233-1252G>A		intron_variant	Intron 3 of 5	3		ENSP00000378341.1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33295 AN: 152088 Hom.: 4020 Cov.: 33

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.0377

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.219 AC: 33315 AN: 152206 Hom.: 4023 Cov.: 33 AF XY: 0.215 AC XY: 16008 AN XY: 74424

African (AFR) AF: 0.305 AC: 12684 AN: 41522

American (AMR) AF: 0.156 AC: 2382 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 862 AN: 3472

East Asian (EAS) AF: 0.0374 AC: 194 AN: 5190

South Asian (SAS) AF: 0.154 AC: 742 AN: 4830

European-Finnish (FIN) AF: 0.184 AC: 1944 AN: 10588

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13889 AN: 67986

Other (OTH) AF: 0.218 AC: 461 AN: 2116

Alfa AF: 0.204 Hom.: 1701

Bravo AF: 0.220

Asia WGS AF: 0.104 AC: 361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.59
DANN	Benign	0.33
PhyloP100		-0.20
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: rs13017044; hg19: chr2-46233349;