rs12712969

Variant names:

• chr2-46105030-C-T
• rs12712969
• NM_005400.3:c.1592+18668C>T

Variant summary

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

The NM_005400.3(PRKCE):​c.1592+18668C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 139,374 control chromosomes in the GnomAD database, including 27,168 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 0.64 (27168 hom., cov: 27)
• Consequence: PRKCE NM_005400.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 6 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005400.3. 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
	PRKCE	NM_005400.3	MANE Select	c.1592+18668C>T		intron	N/A	NP_005391.1	Q02156

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCE	ENST00000306156.8	TSL:1 MANE Select	c.1592+18668C>T		intron	N/A	ENSP00000306124.3	Q02156
	PRKCE	ENST00000872579.1		c.1181+18668C>T		intron	N/A	ENSP00000542638.1
	PRKCE	ENST00000469753.5	TSL:3	n.679+18668C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.644 AC: 89768 AN: 139284 Hom.: 27159 Cov.: 27

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.698

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.664

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

GnomAD4 genome AF: 0.644 AC: 89812 AN: 139374 Hom.: 27168 Cov.: 27 AF XY: 0.646 AC XY: 43821 AN XY: 67842

African (AFR) AF: 0.513 AC: 19792 AN: 38562

American (AMR) AF: 0.667 AC: 8956 AN: 13422

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 1951 AN: 3170

East Asian (EAS) AF: 0.751 AC: 3440 AN: 4580

South Asian (SAS) AF: 0.690 AC: 2847 AN: 4128

European-Finnish (FIN) AF: 0.728 AC: 6862 AN: 9420

Middle Eastern (MID) AF: 0.682 AC: 187 AN: 274

European-Non Finnish (NFE) AF: 0.694 AC: 43756 AN: 63010

Other (OTH) AF: 0.666 AC: 1270 AN: 1908

Alfa AF: 0.741 Hom.: 95810

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.17
PhyloP100		-1.3
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: rs12712969; hg19: chr2-46332169;