rs3783782

Variant names:

• chr14-61473957-G-A
• rs3783782
• NM_006255.5:c.1279-11545G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006255.5(PRKCH):​c.1279-11545G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0199 in 151,582 control chromosomes in the GnomAD database, including 233 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 0.020 (233 hom., cov: 31)
• Consequence: PRKCH NM_006255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.749
• Publications: 22 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCH	NM_006255.5	c.1279-11545G>A		intron_variant	Intron 9 of 13	ENST00000332981.11	NP_006246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCH	ENST00000332981.11	c.1279-11545G>A		intron_variant	Intron 9 of 13	1	NM_006255.5	ENSP00000329127.5

Frequencies

GnomAD3 genomes AF: 0.0199 AC: 3010 AN: 151466 Hom.: 233 Cov.: 31

Gnomad AFR AF: 0.00258

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00927

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.0286

Gnomad FIN AF: 0.0325

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0110

Gnomad OTH AF: 0.0212

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

GnomAD4 genome AF: 0.0199 AC: 3009 AN: 151582 Hom.: 233 Cov.: 31 AF XY: 0.0221 AC XY: 1637 AN XY: 73996

African (AFR) AF: 0.00257 AC: 106 AN: 41262

American (AMR) AF: 0.00925 AC: 141 AN: 15238

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

East Asian (EAS) AF: 0.282 AC: 1453 AN: 5158

South Asian (SAS) AF: 0.0286 AC: 137 AN: 4794

European-Finnish (FIN) AF: 0.0325 AC: 338 AN: 10410

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

European-Non Finnish (NFE) AF: 0.0110 AC: 745 AN: 67944

Other (OTH) AF: 0.0243 AC: 51 AN: 2100

Alfa AF: 0.0191 Hom.: 6

Bravo AF: 0.0184

Asia WGS AF: 0.136 AC: 473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.92
DANN	Benign	0.36
PhyloP100		-0.75
Mutation Taster		=100/0	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: rs3783782; hg19: chr14-61940675;