chr2-46128709-C-A

Variant names:

• chr2-46128709-C-A
• rs13008603
• NM_005400.3:c.1593-16384C>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.1593-16384C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,210 control chromosomes in the GnomAD database, including 960 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 0.10 (960 hom., cov: 32)
• Consequence: PRKCE NM_005400.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• Publications: 14 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=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCE	NM_005400.3	MANE Select	c.1593-16384C>A		intron	N/A	NP_005391.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCE	ENST00000306156.8	TSL:1 MANE Select	c.1593-16384C>A		intron	N/A	ENSP00000306124.3
	PRKCE	ENST00000469753.5	TSL:3	n.680-16384C>A		intron	N/A
	PRKCE	ENST00000480633.1	TSL:2	n.359-16384C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15506 AN: 152092 Hom.: 959 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0720

Gnomad ASJ AF: 0.0902

Gnomad EAS AF: 0.0275

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0559

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0824

Gnomad OTH AF: 0.0956

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

GnomAD4 genome AF: 0.102 AC: 15520 AN: 152210 Hom.: 960 Cov.: 32 AF XY: 0.100 AC XY: 7469 AN XY: 74414

African (AFR) AF: 0.164 AC: 6827 AN: 41524

American (AMR) AF: 0.0718 AC: 1098 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0902 AC: 313 AN: 3470

East Asian (EAS) AF: 0.0276 AC: 143 AN: 5186

South Asian (SAS) AF: 0.131 AC: 634 AN: 4824

European-Finnish (FIN) AF: 0.0559 AC: 592 AN: 10598

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0824 AC: 5601 AN: 68002

Other (OTH) AF: 0.0946 AC: 200 AN: 2114

Alfa AF: 0.0898 Hom.: 1271

Bravo AF: 0.102

Asia WGS AF: 0.0950 AC: 331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.0
DANN	Benign	0.81
PhyloP100		0.061
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: rs13008603; hg19: chr2-46355848;