rs1088680

Positions:

• chr14-61530508-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_006255.5(PRKCH):​c.1674C>T​(p.Asn558=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.825 in 1,611,584 control chromosomes in the GnomAD database, including 558,056 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 0.72 (42659 hom., cov: 31)
  • Exomes 𝑓: 0.84 (515397 hom.)
• Consequence: PRKCH NM_006255.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11

Genes affected

PRKCH (HGNC:9403): (protein kinase C eta) 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. It is a calcium-independent and phospholipids-dependent protein kinase. It is predominantly expressed in epithelial tissues and has been shown to reside specifically in the cell nucleus. This protein kinase can regulate keratinocyte differentiation by activating the MAP kinase MAPK13 (p38delta)-activated protein kinase cascade that targets CCAAT/enhancer-binding protein alpha (CEBPA). It is also found to mediate the transcription activation of the transglutaminase 1 (TGM1) gene. Mutations in this gene are associated with susceptibility to cerebral infarction. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP7: Synonymous conserved (PhyloP=-2.11 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCH	NM_006255.5	c.1674C>T	p.Asn558=	synonymous_variant	12/14	ENST00000332981.11	NP_006246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCH	ENST00000332981.11	c.1674C>T	p.Asn558=	synonymous_variant	12/14	1	NM_006255.5	ENSP00000329127	P1

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109303 AN: 151876 Hom.: 42649 Cov.: 31

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.935

Gnomad AMR AF: 0.850

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.812

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.757

GnomAD3 exomes AF: 0.809 AC: 201970 AN: 249720 Hom.: 83969 AF XY: 0.817 AC XY: 110240 AN XY: 134966

Gnomad AFR exome AF: 0.380

Gnomad AMR exome AF: 0.881

Gnomad ASJ exome AF: 0.915

Gnomad EAS exome AF: 0.658

Gnomad SAS exome AF: 0.815

Gnomad FIN exome AF: 0.820

Gnomad NFE exome AF: 0.858

Gnomad OTH exome AF: 0.847

GnomAD4 exome AF: 0.836 AC: 1220656 AN: 1459590 Hom.: 515397 Cov.: 59 AF XY: 0.838 AC XY: 608406 AN XY: 725996

Gnomad4 AFR exome AF: 0.368

Gnomad4 AMR exome AF: 0.877

Gnomad4 ASJ exome AF: 0.912

Gnomad4 EAS exome AF: 0.703

Gnomad4 SAS exome AF: 0.820

Gnomad4 FIN exome AF: 0.823

Gnomad4 NFE exome AF: 0.855

Gnomad4 OTH exome AF: 0.814

GnomAD4 genome AF: 0.719 AC: 109341 AN: 151994 Hom.: 42659 Cov.: 31 AF XY: 0.722 AC XY: 53647 AN XY: 74282

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.850

Gnomad4 ASJ AF: 0.908

Gnomad4 EAS AF: 0.671

Gnomad4 SAS AF: 0.813

Gnomad4 FIN AF: 0.818

Gnomad4 NFE AF: 0.858

Gnomad4 OTH AF: 0.756

Alfa AF: 0.830 Hom.: 87125

Bravo AF: 0.706

Asia WGS AF: 0.686 AC: 2388 AN: 3478

EpiCase AF: 0.867

EpiControl AF: 0.870

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	0.077
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs1088680; hg19: chr14-61997226; COSMIC: COSV60651087; COSMIC: COSV60651087;