2-46086342-C-T

Variant names:

• chr2-46086342-C-T
• rs1143691
• NM_005400.3:c.1572C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_005400.3(PRKCE):​c.1572C>T​(p.His524His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,599,336 control chromosomes in the GnomAD database, including 11,785 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 0.087 (1020 hom., cov: 32)
  • Exomes 𝑓: 0.10 (10765 hom.)
• Consequence: PRKCE NM_005400.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12
• Publications: 10 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP7: Synonymous conserved (PhyloP=2.12 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCE	NM_005400.3	c.1572C>T	p.His524His	synonymous_variant	Exon 11 of 15	ENST00000306156.8	NP_005391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCE	ENST00000306156.8	c.1572C>T	p.His524His	synonymous_variant	Exon 11 of 15	1	NM_005400.3	ENSP00000306124.3
PRKCE	ENST00000469753.5	n.659C>T		non_coding_transcript_exon_variant	Exon 2 of 4	3
PRKCE	ENST00000480633.1	n.338C>T		non_coding_transcript_exon_variant	Exon 2 of 4	2

Frequencies

GnomAD3 genomes AF: 0.0869 AC: 13223 AN: 152118 Hom.: 1015 Cov.: 32

Gnomad AFR AF: 0.0216

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0715

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.0809

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0880

Gnomad OTH AF: 0.0880

GnomAD2 exomes AF: 0.138 AC: 32611 AN: 236692 AF XY: 0.139

Gnomad AFR exome AF: 0.0202

Gnomad AMR exome AF: 0.181

Gnomad ASJ exome AF: 0.0779

Gnomad EAS exome AF: 0.426

Gnomad FIN exome AF: 0.0882

Gnomad NFE exome AF: 0.0878

Gnomad OTH exome AF: 0.116

GnomAD4 exome AF: 0.105 AC: 151763 AN: 1447100 Hom.: 10765 Cov.: 32 AF XY: 0.108 AC XY: 77661 AN XY: 720254

African (AFR) AF: 0.0149 AC: 498 AN: 33466

American (AMR) AF: 0.172 AC: 7698 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.0754 AC: 1971 AN: 26126

East Asian (EAS) AF: 0.366 AC: 14519 AN: 39688

South Asian (SAS) AF: 0.209 AC: 18032 AN: 86228

European-Finnish (FIN) AF: 0.0962 AC: 3767 AN: 39138

Middle Eastern (MID) AF: 0.0689 AC: 397 AN: 5762

European-Non Finnish (NFE) AF: 0.0882 AC: 98078 AN: 1111712

Other (OTH) AF: 0.113 AC: 6803 AN: 60286

GnomAD4 genome AF: 0.0869 AC: 13233 AN: 152236 Hom.: 1020 Cov.: 32 AF XY: 0.0912 AC XY: 6786 AN XY: 74426

African (AFR) AF: 0.0215 AC: 893 AN: 41558

American (AMR) AF: 0.122 AC: 1859 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0715 AC: 248 AN: 3470

East Asian (EAS) AF: 0.400 AC: 2063 AN: 5162

South Asian (SAS) AF: 0.228 AC: 1099 AN: 4818

European-Finnish (FIN) AF: 0.0809 AC: 858 AN: 10606

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0880 AC: 5988 AN: 68012

Other (OTH) AF: 0.0890 AC: 188 AN: 2112

Alfa AF: 0.0875 Hom.: 795

Bravo AF: 0.0885

Asia WGS AF: 0.282 AC: 979 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	8.1
DANN	Benign	0.72
PhyloP100		2.1
Mutation Taster		=96/4	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: rs1143691; hg19: chr2-46313481; COSMIC: COSV60314217;