14-61432121-T-G

Variant names:

• chr14-61432121-T-G
• rs17098356
• NM_006255.5:c.428-10990T>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.428-10990T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 151,146 control chromosomes in the GnomAD database, including 36,865 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 0.70 (36865 hom., cov: 28)
• Consequence: PRKCH NM_006255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 5 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.706 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCH	NM_006255.5	MANE Select	c.428-10990T>G		intron	N/A	NP_006246.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCH	ENST00000332981.11	TSL:1 MANE Select	c.428-10990T>G		intron	N/A	ENSP00000329127.5
	PRKCH	ENST00000555082.6	TSL:1	c.-56-10990T>G		intron	N/A	ENSP00000450981.1
	PRKCH	ENST00000557585.5	TSL:5	c.-56-10990T>G		intron	N/A	ENSP00000451930.1

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105183 AN: 151032 Hom.: 36831 Cov.: 28

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.665

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

GnomAD4 genome AF: 0.696 AC: 105270 AN: 151146 Hom.: 36865 Cov.: 28 AF XY: 0.695 AC XY: 51279 AN XY: 73822

African (AFR) AF: 0.702 AC: 28867 AN: 41148

American (AMR) AF: 0.566 AC: 8610 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 2526 AN: 3466

East Asian (EAS) AF: 0.726 AC: 3732 AN: 5142

South Asian (SAS) AF: 0.709 AC: 3380 AN: 4768

European-Finnish (FIN) AF: 0.745 AC: 7681 AN: 10312

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.711 AC: 48212 AN: 67814

Other (OTH) AF: 0.669 AC: 1400 AN: 2094

Alfa AF: 0.694 Hom.: 14258

Bravo AF: 0.684

Asia WGS AF: 0.710 AC: 2458 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.29
DANN	Benign	0.62
PhyloP100		-1.2
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: rs17098356; hg19: chr14-61898839;