chr10-6485181-G-A

Position:

chr10-6485181-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

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

BP6

Variant 10-6485181-G-A is Benign according to our data. Variant chr10-6485181-G-A is described in ClinVar as [Benign]. Clinvar id is 586982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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/exons	MANE	UniProt
PRKCQ	NM_006257.5 linkuse as main transcript	c.989C>T	p.Pro330Leu	missense_variant	10/18	ENST00000263125.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCQ	ENST00000263125.10 linkuse as main transcript	c.989C>T	p.Pro330Leu	missense_variant	10/18	1	NM_006257.5	P1	Q04759-1
PRKCQ	ENST00000397176.6 linkuse as main transcript	c.989C>T	p.Pro330Leu	missense_variant	10/17	5			Q04759-2
PRKCQ	ENST00000539722.5 linkuse as main transcript	c.614C>T	p.Pro205Leu	missense_variant	9/17	2			Q04759-3

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

GnomAD3 exomes

AF:

0.305

AC:

76764

AN:

251410

Hom.:

12789

AF XY:

0.305

AC XY:

41410

AN XY:

135870

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 SAS exome

AF:

0.432

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

Gnomad4 AFR exome

AF:

0.366

Gnomad4 AMR exome

AF:

0.378

Gnomad4 ASJ exome

AF:

0.255

Gnomad4 EAS exome

AF:

0.440

Gnomad4 SAS exome

AF:

0.431

Gnomad4 FIN exome

AF:

0.196

Gnomad4 NFE exome

AF:

0.252

Gnomad4 OTH exome

AF:

0.290

GnomAD4 genome

AF:

0.300

AC:

45628

AN:

151858

Hom.:

7246

Cov.:

AF XY:

0.302

AC XY:

22403

AN XY:

74210

show subpopulations

Gnomad4 AFR

AF:

0.363

Gnomad4 AMR

AF:

0.351

Gnomad4 ASJ

AF:

0.253

Gnomad4 EAS

AF:

0.421

Gnomad4 SAS

AF:

0.437

Gnomad4 FIN

AF:

0.198

Gnomad4 NFE

AF:

0.252

Gnomad4 OTH

AF:

0.295

Alfa

AF:

0.269

Hom.:

10942

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 30, 2020	This variant is associated with the following publications: (PMID: 30828974) -

Inflammatory bowel disease 1

Pathogenic:1

Pathogenic, no assertion criteria provided

case-control

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

- -

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

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;.

MutationTaster

Benign

1.0

P;P;P

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over