rs2230501

Variant names:

• chr14-61457523-A-C
• rs2230501
• NM_006255.5:c.1122A>C

Your query was ambiguous. Multiple possible variants found:

• chr14-61457523-A-C
• chr14-61457523-A-G
• chr14-61457523-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006255.5(PRKCH):​c.1122A>C​(p.Val374Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 1,614,038 control chromosomes in the GnomAD database, including 1,583 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 0.019 (190 hom., cov: 32)
  • Exomes 𝑓: 0.018 (1393 hom.)
• Consequence: PRKCH NM_006255.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400
• Publications: 6 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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=-0.004 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCH	NM_006255.5	c.1122A>C	p.Val374Val	synonymous_variant	Exon 9 of 14	ENST00000332981.11	NP_006246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCH	ENST00000332981.11	c.1122A>C	p.Val374Val	synonymous_variant	Exon 9 of 14	1	NM_006255.5	ENSP00000329127.5

Frequencies

GnomAD3 genomes AF: 0.0187 AC: 2852 AN: 152146 Hom.: 188 Cov.: 32

Gnomad AFR AF: 0.00234

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00929

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.0227

Gnomad FIN AF: 0.0327

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.0201

GnomAD2 exomes AF: 0.0308 AC: 7739 AN: 251304 AF XY: 0.0299

Gnomad AFR exome AF: 0.00197

Gnomad AMR exome AF: 0.00613

Gnomad ASJ exome AF: 0.0101

Gnomad EAS exome AF: 0.268

Gnomad FIN exome AF: 0.0357

Gnomad NFE exome AF: 0.0106

Gnomad OTH exome AF: 0.0181

GnomAD4 exome AF: 0.0180 AC: 26311 AN: 1461772 Hom.: 1393 Cov.: 32 AF XY: 0.0177 AC XY: 12889 AN XY: 727188

African (AFR) AF: 0.00167 AC: 56 AN: 33476

American (AMR) AF: 0.00653 AC: 292 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00911 AC: 238 AN: 26132

East Asian (EAS) AF: 0.242 AC: 9587 AN: 39694

South Asian (SAS) AF: 0.0128 AC: 1108 AN: 86254

European-Finnish (FIN) AF: 0.0322 AC: 1719 AN: 53416

Middle Eastern (MID) AF: 0.00434 AC: 25 AN: 5764

European-Non Finnish (NFE) AF: 0.0105 AC: 11729 AN: 1111926

Other (OTH) AF: 0.0258 AC: 1557 AN: 60388

GnomAD4 genome AF: 0.0188 AC: 2855 AN: 152266 Hom.: 190 Cov.: 32 AF XY: 0.0211 AC XY: 1569 AN XY: 74436

African (AFR) AF: 0.00233 AC: 97 AN: 41578

American (AMR) AF: 0.00928 AC: 142 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 36 AN: 3470

East Asian (EAS) AF: 0.258 AC: 1329 AN: 5160

South Asian (SAS) AF: 0.0227 AC: 109 AN: 4808

European-Finnish (FIN) AF: 0.0327 AC: 347 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0109 AC: 742 AN: 68018

Other (OTH) AF: 0.0242 AC: 51 AN: 2110

Alfa AF: 0.00696 Hom.: 3

Bravo AF: 0.0170

Asia WGS AF: 0.135 AC: 468 AN: 3478

EpiCase AF: 0.00960

EpiControl AF: 0.00865

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	5.1
DANN	Benign	0.69
PhyloP100		-0.0040
Mutation Taster		=98/2	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: rs2230501; hg19: chr14-61924241; COSMIC: COSV60646813; COSMIC: COSV60646813;