chr14-61525314-C-T

Variant names:

• chr14-61525314-C-T
• rs1111108
• NM_006255.5:c.1434-3761C>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.1434-3761C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.983 in 152,316 control chromosomes in the GnomAD database, including 73,623 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 0.98 (73619 hom., cov: 31)
  • Exomes 𝑓: 1.0 (4 hom.)
• Consequence: PRKCH NM_006255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• 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]

ENSG00000308763 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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.1434-3761C>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.1434-3761C>T		intron	N/A	ENSP00000329127.5
	PRKCH	ENST00000555082.6	TSL:1	c.951-3761C>T		intron	N/A	ENSP00000450981.1
	PRKCH	ENST00000555185.5	TSL:3	c.138-3761C>T		intron	N/A	ENSP00000451871.1

Frequencies

GnomAD3 genomes AF: 0.983 AC: 149584 AN: 152190 Hom.: 73557 Cov.: 31

Gnomad AFR AF: 0.941

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.993

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.981

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.982

GnomAD4 exome AF: 1.00 AC: 8 AN: 8 Hom.: 4 AF XY: 1.00 AC XY: 6 AN XY: 6

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 6 AN: 6

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.983 AC: 149704 AN: 152308 Hom.: 73619 Cov.: 31 AF XY: 0.984 AC XY: 73242 AN XY: 74468

African (AFR) AF: 0.941 AC: 39106 AN: 41544

American (AMR) AF: 0.993 AC: 15196 AN: 15298

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5192 AN: 5192

South Asian (SAS) AF: 1.00 AC: 4826 AN: 4828

European-Finnish (FIN) AF: 1.00 AC: 10618 AN: 10618

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68020 AN: 68038

Other (OTH) AF: 0.982 AC: 2074 AN: 2112

Alfa AF: 0.991 Hom.: 14687

Bravo AF: 0.980

Asia WGS AF: 0.997 AC: 3468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.056
DANN	Benign	0.60
PhyloP100		-1.9
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: rs1111108; hg19: chr14-61992032;