rs10483735

Variant names:

• chr14-61479521-C-T
• rs10483735
• NM_006255.5:c.1279-5981C>T

Variant summary

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

The NM_006255.5(PRKCH):​c.1279-5981C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0192 in 152,258 control chromosomes in the GnomAD database, including 165 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 (165 hom., cov: 32)
• Consequence: PRKCH NM_006255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.634
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.227 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.1279-5981C>T		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.1279-5981C>T		intron	N/A	ENSP00000329127.5
	PRKCH	ENST00000555082.6	TSL:1	c.796-5981C>T		intron	N/A	ENSP00000450981.1
	PRKCH	ENST00000555185.5	TSL:3	c.-18-5981C>T		intron	N/A	ENSP00000451871.1

Frequencies

GnomAD3 genomes AF: 0.0192 AC: 2927 AN: 152140 Hom.: 165 Cov.: 32

Gnomad AFR AF: 0.00261

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00674

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.0550

Gnomad FIN AF: 0.0335

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0114

Gnomad OTH AF: 0.0206

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

GnomAD4 genome AF: 0.0192 AC: 2924 AN: 152258 Hom.: 165 Cov.: 32 AF XY: 0.0217 AC XY: 1612 AN XY: 74454

African (AFR) AF: 0.00260 AC: 108 AN: 41544

American (AMR) AF: 0.00673 AC: 103 AN: 15298

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

East Asian (EAS) AF: 0.238 AC: 1229 AN: 5162

South Asian (SAS) AF: 0.0551 AC: 266 AN: 4830

European-Finnish (FIN) AF: 0.0335 AC: 356 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0114 AC: 776 AN: 68022

Other (OTH) AF: 0.0227 AC: 48 AN: 2112

Alfa AF: 0.0122 Hom.: 8

Bravo AF: 0.0162

Asia WGS AF: 0.128 AC: 444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.9
DANN	Benign	0.53
PhyloP100		0.63
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: rs10483735; hg19: chr14-61946239;