rs10483741

Variant names:

• chr14-61522983-A-G
• rs10483741
• NM_006255.5:c.1434-6092A>G

Variant summary

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

The NM_006255.5(PRKCH):​c.1434-6092A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,226 control chromosomes in the GnomAD database, including 11,063 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 0.35 (11063 hom., cov: 33)
• Consequence: PRKCH NM_006255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.217
• Publications: 1 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]

ENSG00000308763 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006255.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCH	NM_006255.5	MANE Select	c.1434-6092A>G		intron	N/A	NP_006246.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCH	ENST00000332981.11	TSL:1 MANE Select	c.1434-6092A>G		intron	N/A	ENSP00000329127.5	P24723-1
	PRKCH	ENST00000555082.6	TSL:1	c.951-6092A>G		intron	N/A	ENSP00000450981.1	P24723-2
	PRKCH	ENST00000555185.5	TSL:3	c.138-6092A>G		intron	N/A	ENSP00000451871.1	G3V4L3

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52873 AN: 152108 Hom.: 11022 Cov.: 33

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.348 AC: 52971 AN: 152226 Hom.: 11063 Cov.: 33 AF XY: 0.346 AC XY: 25717 AN XY: 74416

African (AFR) AF: 0.594 AC: 24651 AN: 41516

American (AMR) AF: 0.230 AC: 3525 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 874 AN: 3470

East Asian (EAS) AF: 0.344 AC: 1786 AN: 5194

South Asian (SAS) AF: 0.364 AC: 1758 AN: 4826

European-Finnish (FIN) AF: 0.243 AC: 2580 AN: 10600

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16935 AN: 67998

Other (OTH) AF: 0.322 AC: 681 AN: 2116

Alfa AF: 0.315 Hom.: 1179

Bravo AF: 0.353

Asia WGS AF: 0.382 AC: 1328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.66
PhyloP100		-0.22
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: rs10483741; hg19: chr14-61989701;