14-61432121-T-G

Position:

• chr14-61432121-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCH	NM_006255.5	c.428-10990T>G		intron_variant		ENST00000332981.11	NP_006246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCH	ENST00000332981.11	c.428-10990T>G		intron_variant		1	NM_006255.5	ENSP00000329127	P1

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

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.566

Gnomad4 ASJ AF: 0.729

Gnomad4 EAS AF: 0.726

Gnomad4 SAS AF: 0.709

Gnomad4 FIN AF: 0.745

Gnomad4 NFE AF: 0.711

Gnomad4 OTH AF: 0.669

Alfa AF: 0.693 Hom.: 9103

Bravo AF: 0.684

Asia WGS AF: 0.710 AC: 2458 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.29
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs17098356; hg19: chr14-61898839;