14-61547815-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_006255.5(PRKCH):c.1834C>T(p.Pro612Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000725 in 1,614,202 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00071 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00073 ( 2 hom. )

Consequence

PRKCH
NM_006255.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.98

Publications

3 publications found

Variant links:

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]

PRKCH links:

ENSG00000258989 (HGNC:):

ENSG00000258989 links:

LINC01303 (HGNC:50470): (long intergenic non-protein coding RNA 1303)

LINC01303 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015982598).

BP6

Variant 14-61547815-C-T is Benign according to our data. Variant chr14-61547815-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3047670.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 108 AD gene.

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.1834C>T	p.Pro612Ser	missense	Exon 13 of 14	NP_006246.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRKCH	ENST00000332981.11	TSL:1 MANE Select	c.1834C>T	p.Pro612Ser	missense	Exon 13 of 14	ENSP00000329127.5	P24723-1
PRKCH	ENST00000555082.6	TSL:1	c.1351C>T	p.Pro451Ser	missense	Exon 13 of 14	ENSP00000450981.1	P24723-2
ENSG00000258989	ENST00000556347.1	TSL:4	c.346C>T	p.Pro116Ser	missense	Exon 3 of 4	ENSP00000452401.1	H0YJX3

Frequencies

GnomAD3 genomes

AF:

0.000703

AC:

107

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000947

AC:

238

AN:

251386

AF XY:

0.000898

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00411

Gnomad NFE exome

AF:

0.00112

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000727

AC:

1063

AN:

1461856

Hom.:

Cov.:

AF XY:

0.000740

AC XY:

538

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.0000894

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000417

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00565

AC:

302

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000616

AC:

685

AN:

1111998

Other (OTH)

AF:

0.000580

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

112

169

225

281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000709

AC:

108

AN:

152346

Hom.:

Cov.:

AF XY:

0.000805

AC XY:

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41576

American (AMR)

AF:

0.0000653

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000621

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00471

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000691

AC:

AN:

68034

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000569

Hom.:

Bravo

AF:

0.000325

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00105

AC:

128

EpiCase

AF:

0.000709

EpiControl

AF:

0.000593

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

PRKCH-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.021

MetaRNN

Benign

0.016

MetaSVM

Benign

-0.67

MutationAssessor

Uncertain

2.3

PhyloP100

2.0

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-4.4

REVEL

Benign

0.22

Sift

Benign

0.063

Sift4G

Benign

0.13

Polyphen

0.38

Vest4

0.36

MVP

0.59

MPC

0.55

ClinPred

0.041

GERP RS

6.0

Varity_R

0.28

gMVP

0.56

Mutation Taster

=40/60

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over