rs1088680

Variant names:

• chr14-61530508-C-T
• rs1088680
• NM_006255.5:c.1674C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP7 BA1

The NM_006255.5(PRKCH):​c.1674C>T​(p.Asn558Asn) 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. 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
• Publications: 26 publications found

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]

ENSG00000258989 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• 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 rank	MANE	Protein	UniProt
PRKCH	NM_006255.5	c.1674C>T	p.Asn558Asn	synonymous_variant	Exon 12 of 14	ENST00000332981.11	NP_006246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCH	ENST00000332981.11	c.1674C>T	p.Asn558Asn	synonymous_variant	Exon 12 of 14	1	NM_006255.5	ENSP00000329127.5
ENSG00000258989	ENST00000556347.1	c.186C>T	p.Asn62Asn	synonymous_variant	Exon 2 of 4	4		ENSP00000452401.1

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

GnomAD2 exomes AF: 0.809 AC: 201970 AN: 249720 AF XY: 0.817

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 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

African (AFR) AF: 0.368 AC: 12297 AN: 33444

American (AMR) AF: 0.877 AC: 38911 AN: 44372

Ashkenazi Jewish (ASJ) AF: 0.912 AC: 23815 AN: 26120

East Asian (EAS) AF: 0.703 AC: 27867 AN: 39628

South Asian (SAS) AF: 0.820 AC: 70137 AN: 85572

European-Finnish (FIN) AF: 0.823 AC: 43947 AN: 53398

Middle Eastern (MID) AF: 0.878 AC: 5060 AN: 5762

European-Non Finnish (NFE) AF: 0.855 AC: 949515 AN: 1110972

Other (OTH) AF: 0.814 AC: 49107 AN: 60322

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

African (AFR) AF: 0.390 AC: 16144 AN: 41370

American (AMR) AF: 0.850 AC: 12993 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3152 AN: 3472

East Asian (EAS) AF: 0.671 AC: 3461 AN: 5158

South Asian (SAS) AF: 0.813 AC: 3917 AN: 4820

European-Finnish (FIN) AF: 0.818 AC: 8649 AN: 10578

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.858 AC: 58317 AN: 68000

Other (OTH) AF: 0.756 AC: 1593 AN: 2108

Alfa AF: 0.815 Hom.: 169259

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
PhyloP100		-2.1
Mutation Taster		=91/9	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: rs1088680; hg19: chr14-61997226; COSMIC: COSV60651087; COSMIC: COSV60651087;