chr14-61541347-C-T

Variant names:

• chr14-61541347-C-T
• rs2246695
• NM_006255.5:c.1762-6396C>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.1762-6396C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 152,240 control chromosomes in the GnomAD database, including 34,332 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 0.60 (34332 hom., cov: 34)
• Consequence: PRKCH NM_006255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270
• Publications: 4 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]

ENSG00000258989 (HGNC:):

PRKCH-AS2 (HGNC:58291):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.818 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.1762-6396C>T		intron	N/A	NP_006246.2
	PRKCH-AS2	NR_188136.1		n.392-3441G>A		intron	N/A
	PRKCH-AS2	NR_188137.1		n.392-2160G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCH	ENST00000332981.11	TSL:1 MANE Select	c.1762-6396C>T		intron	N/A	ENSP00000329127.5	P24723-1
	PRKCH	ENST00000555082.6	TSL:1	c.1279-6396C>T		intron	N/A	ENSP00000450981.1	P24723-2
	ENSG00000258989	ENST00000556347.1	TSL:4	c.274-6396C>T		intron	N/A	ENSP00000452401.1	H0YJX3

Frequencies

GnomAD3 genomes AF: 0.605 AC: 92013 AN: 152122 Hom.: 34331 Cov.: 34

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.931

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.848

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.774

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.646

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

GnomAD4 genome AF: 0.604 AC: 92015 AN: 152240 Hom.: 34332 Cov.: 34 AF XY: 0.604 AC XY: 44937 AN XY: 74426

African (AFR) AF: 0.162 AC: 6740 AN: 41532

American (AMR) AF: 0.669 AC: 10241 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 2944 AN: 3472

East Asian (EAS) AF: 0.360 AC: 1862 AN: 5174

South Asian (SAS) AF: 0.626 AC: 3016 AN: 4820

European-Finnish (FIN) AF: 0.824 AC: 8743 AN: 10614

Middle Eastern (MID) AF: 0.767 AC: 224 AN: 292

European-Non Finnish (NFE) AF: 0.824 AC: 56031 AN: 68008

Other (OTH) AF: 0.647 AC: 1367 AN: 2112

Alfa AF: 0.760 Hom.: 85457

Bravo AF: 0.573

Asia WGS AF: 0.490 AC: 1710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.7
DANN	Benign	0.70
PhyloP100		0.027
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: rs2246695; hg19: chr14-62008065;