NM_005400.3:c.349-36420C>T

Variant names:

• chr2-45806580-C-T
• rs4953260
• NM_005400.3:c.349-36420C>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.349-36420C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 152,026 control chromosomes in the GnomAD database, including 15,320 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 0.40 (15320 hom., cov: 32)
• Consequence: PRKCE NM_005400.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.437
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCE	NM_005400.3	c.349-36420C>T		intron_variant	Intron 1 of 14	ENST00000306156.8	NP_005391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCE	ENST00000306156.8	c.349-36420C>T		intron_variant	Intron 1 of 14	1	NM_005400.3	ENSP00000306124.3

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60488 AN: 151908 Hom.: 15289 Cov.: 32

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.398 AC: 60559 AN: 152026 Hom.: 15320 Cov.: 32 AF XY: 0.402 AC XY: 29881 AN XY: 74316

African (AFR) AF: 0.708 AC: 29337 AN: 41446

American (AMR) AF: 0.423 AC: 6462 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1049 AN: 3472

East Asian (EAS) AF: 0.402 AC: 2080 AN: 5168

South Asian (SAS) AF: 0.385 AC: 1854 AN: 4814

European-Finnish (FIN) AF: 0.314 AC: 3317 AN: 10558

Middle Eastern (MID) AF: 0.349 AC: 102 AN: 292

European-Non Finnish (NFE) AF: 0.227 AC: 15419 AN: 67980

Other (OTH) AF: 0.376 AC: 793 AN: 2108

Alfa AF: 0.287 Hom.: 5969

Bravo AF: 0.424

Asia WGS AF: 0.450 AC: 1566 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.3
DANN	Benign	0.37
PhyloP100		0.44
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: rs4953260; hg19: chr2-46033719;