rs3783799

Positions:

• chr14-61452498-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006255.5(PRKCH):​c.833-728C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 152,298 control chromosomes in the GnomAD database, including 185 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 (185 hom., cov: 32)
• Consequence: PRKCH NM_006255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• 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/exons	MANE	UniProt
PRKCH	NM_006255.5	c.833-728C>T		intron_variant		ENST00000332981.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCH	ENST00000332981.11	c.833-728C>T		intron_variant		1	NM_006255.5	P1

Frequencies

GnomAD3 genomes AF: 0.0187 AC: 2846 AN: 152180 Hom.: 186 Cov.: 32

Gnomad AFR AF: 0.00236

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00838

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.0327

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.0196

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

GnomAD4 genome AF: 0.0186 AC: 2838 AN: 152298 Hom.: 185 Cov.: 32 AF XY: 0.0212 AC XY: 1576 AN XY: 74472

Gnomad4 AFR AF: 0.00236

Gnomad4 AMR AF: 0.00836

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.0230

Gnomad4 FIN AF: 0.0327

Gnomad4 NFE AF: 0.0109

Gnomad4 OTH AF: 0.0198

Alfa AF: 0.0117 Hom.: 35

Bravo AF: 0.0169

Asia WGS AF: 0.120 AC: 416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	10
DANN	Benign	0.69

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: rs3783799; hg19: chr14-61919216;