rs2236379

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006257.5(PRKCQ):c.989C>T(p.Pro330Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 1,612,426 control chromosomes in the GnomAD database, including 65,086 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.30 ( 7246 hom., cov: 31)

Exomes 𝑓: 0.27 ( 57840 hom. )

Consequence

PRKCQ
NM_006257.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:2

Conservation

PhyloP100: 0.729

Publications

48 publications found

Variant links:

Genes affected

PRKCQ (HGNC:9410): (protein kinase C theta) 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. The protein encoded by this gene is one of the PKC family members. It is a calcium-independent and phospholipid-dependent protein kinase. This kinase is important for T-cell activation. It is required for the activation of the transcription factors NF-kappaB and AP-1, and may link the T cell receptor (TCR) signaling complex to the activation of the transcription factors. [provided by RefSeq, Jul 2008]

PRKCQ links:

ENSG00000302067 (HGNC:):

ENSG00000302067 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=8.043051E-4).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCQ	NM_006257.5 link	c.989C>T	p.Pro330Leu	missense_variant	Exon 10 of 18	ENST00000263125.10	NP_006248.1	Q04759-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PRKCQ	ENST00000263125.10 link	c.989C>T	p.Pro330Leu	missense_variant	Exon 10 of 18	1	NM_006257.5	ENSP00000263125.5	Q04759-1
PRKCQ	ENST00000397176.6 link	c.989C>T	p.Pro330Leu	missense_variant	Exon 10 of 17	5		ENSP00000380361.2	Q04759-2
PRKCQ	ENST00000539722.5 link	c.614C>T	p.Pro205Leu	missense_variant	Exon 9 of 17	2		ENSP00000441752.1	Q04759-3
ENSG00000302067	ENST00000783835.1 link	n.381+38209G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.301

AC:

45614

AN:

151740

Hom.:

7250

Cov.:

show subpopulations

Gnomad AFR

AF:

0.364

Gnomad AMI

AF:

0.234

Gnomad AMR

AF:

0.351

Gnomad ASJ

AF:

0.253

Gnomad EAS

AF:

0.421

Gnomad SAS

AF:

0.437

Gnomad FIN

AF:

0.198

Gnomad MID

AF:

0.201

Gnomad NFE

AF:

0.252

Gnomad OTH

AF:

0.295

GnomAD2 exomes

AF:

0.305

AC:

76764

AN:

251410

AF XY:

0.305

show subpopulations

Gnomad AFR exome

AF:

0.363

Gnomad AMR exome

AF:

0.386

Gnomad ASJ exome

AF:

0.250

Gnomad EAS exome

AF:

0.414

Gnomad FIN exome

AF:

0.196

Gnomad NFE exome

AF:

0.248

Gnomad OTH exome

AF:

0.282

GnomAD4 exome

AF:

0.274

AC:

400411

AN:

1460568

Hom.:

57840

Cov.:

AF XY:

0.277

AC XY:

201607

AN XY:

726630

show subpopulations

African (AFR)

AF:

0.366

AC:

12254

AN:

33462

American (AMR)

AF:

0.378

AC:

16899

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.255

AC:

6647

AN:

26108

East Asian (EAS)

AF:

0.440

AC:

17445

AN:

39676

South Asian (SAS)

AF:

0.431

AC:

37124

AN:

86194

European-Finnish (FIN)

AF:

0.196

AC:

10447

AN:

53344

Middle Eastern (MID)

AF:

0.307

AC:

1771

AN:

5762

European-Non Finnish (NFE)

AF:

0.252

AC:

280345

AN:

1110990

Other (OTH)

AF:

0.290

AC:

17479

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

14502

29005

43507

58010

72512

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9826

19652

29478

39304

49130

<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:

0.300

AC:

45628

AN:

151858

Hom.:

7246

Cov.:

AF XY:

0.302

AC XY:

22403

AN XY:

74210

show subpopulations

African (AFR)

AF:

0.363

AC:

15033

AN:

41364

American (AMR)

AF:

0.351

AC:

5361

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.253

AC:

876

AN:

3466

East Asian (EAS)

AF:

0.421

AC:

2165

AN:

5138

South Asian (SAS)

AF:

0.437

AC:

2099

AN:

4806

European-Finnish (FIN)

AF:

0.198

AC:

2091

AN:

10546

Middle Eastern (MID)

AF:

0.202

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.252

AC:

17107

AN:

67944

Other (OTH)

AF:

0.295

AC:

624

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1587

3174

4761

6348

7935

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

458

916

1374

1832

2290

<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:

0.271

Hom.:

21287

Bravo

AF:

0.313

TwinsUK

AF:

0.244

AC:

905

ALSPAC

AF:

0.259

AC:

1000

ESP6500AA

AF:

0.348

AC:

1535

ESP6500EA

AF:

0.250

AC:

2147

ExAC

AF:

0.305

AC:

36980

Asia WGS

AF:

0.407

AC:

1418

AN:

3478

EpiCase

AF:

0.262

EpiControl

AF:

0.260

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 30, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 30828974) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Inflammatory bowel disease 1

Pathogenic:1

Lab of Gastroenterology, College of Medicine, First Affiliate Hospital of Zhejiang University

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:case-control

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Benign

2.2

(source)

DANN

Benign

0.32

DEOGEN2

Benign

0.013

T;T;.;.

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.0056

LIST_S2

Benign

0.76

T;T;T;T

MetaRNN

Benign

0.00080

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.35

.;N;N;.

PhyloP100

0.73

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.0

.;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.35

.;T;T;T

Sift4G

Benign

0.44

T;T;T;T

Polyphen

0.0

.;B;B;.

Vest4

0.034

MPC

0.47

ClinPred

0.0026

GERP RS

-2.7

Varity_R

0.026

gMVP

0.18

Mutation Taster

=94/6

disease causing (ClinVar)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over