14-61441358-T-C

Variant names:

• chr14-61441358-T-C
• rs1957893
• NM_006255.5:c.428-1753T>C

Variant summary

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

The NM_006255.5(PRKCH):​c.428-1753T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 152,104 control chromosomes in the GnomAD database, including 46,075 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 0.74 (46075 hom., cov: 31)
• Consequence: PRKCH NM_006255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCH	NM_006255.5	c.428-1753T>C		intron_variant	Intron 2 of 13	ENST00000332981.11	NP_006246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCH	ENST00000332981.11	c.428-1753T>C		intron_variant	Intron 2 of 13	1	NM_006255.5	ENSP00000329127.5

Frequencies

GnomAD3 genomes AF: 0.737 AC: 112035 AN: 151986 Hom.: 46072 Cov.: 31

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.865

Gnomad ASJ AF: 0.917

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.865

Gnomad FIN AF: 0.902

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.774

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

GnomAD4 genome AF: 0.737 AC: 112062 AN: 152104 Hom.: 46075 Cov.: 31 AF XY: 0.742 AC XY: 55165 AN XY: 74360

African (AFR) AF: 0.346 AC: 14324 AN: 41442

American (AMR) AF: 0.865 AC: 13222 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.917 AC: 3183 AN: 3472

East Asian (EAS) AF: 0.604 AC: 3119 AN: 5168

South Asian (SAS) AF: 0.865 AC: 4167 AN: 4820

European-Finnish (FIN) AF: 0.902 AC: 9544 AN: 10582

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.908 AC: 61791 AN: 68018

Other (OTH) AF: 0.771 AC: 1626 AN: 2110

Alfa AF: 0.835 Hom.: 71858

Bravo AF: 0.719

Asia WGS AF: 0.709 AC: 2470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.075
DANN	Benign	0.53
PhyloP100		-1.6
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: rs1957893; hg19: chr14-61908076;