Variant chr10-6479019-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_006257.5(PRKCQ):c.1326G>A(p.Thr442=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00928 in 1,614,094 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0082 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0094 ( 85 hom. )

Consequence

PRKCQ
NM_006257.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.64

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 10-6479019-C-T is Benign according to our data. Variant chr10-6479019-C-T is described in ClinVar as [Benign]. Clinvar id is 784651.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.64 with no splicing effect.

BS2

High AC in GnomAd4 at 1246 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCQ	NM_006257.5 linkuse as main transcript	c.1326G>A	p.Thr442=	synonymous_variant	12/18	ENST00000263125.10	NP_006248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCQ	ENST00000263125.10 linkuse as main transcript	c.1326G>A	p.Thr442=	synonymous_variant	12/18	1	NM_006257.5	ENSP00000263125	P1	Q04759-1
PRKCQ	ENST00000397176.6 linkuse as main transcript	c.1326G>A	p.Thr442=	synonymous_variant	12/17	5		ENSP00000380361		Q04759-2
PRKCQ	ENST00000539722.5 linkuse as main transcript	c.951G>A	p.Thr317=	synonymous_variant	11/17	2		ENSP00000441752		Q04759-3

Frequencies

GnomAD3 genomes

AF:

0.00820

AC:

1247

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00176

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00740

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00270

Gnomad FIN

AF:

0.0175

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0118

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00883

AC:

2219

AN:

251316

Hom.:

AF XY:

0.00881

AC XY:

1197

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.00416

Gnomad ASJ exome

AF:

0.0185

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00193

Gnomad FIN exome

AF:

0.0180

Gnomad NFE exome

AF:

0.0119

Gnomad OTH exome

AF:

0.0108

GnomAD4 exome

AF:

0.00939

AC:

13727

AN:

1461848

Hom.:

Cov.:

AF XY:

0.00930

AC XY:

6763

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00122

Gnomad4 AMR exome

AF:

0.00423

Gnomad4 ASJ exome

AF:

0.0174

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00231

Gnomad4 FIN exome

AF:

0.0182

Gnomad4 NFE exome

AF:

0.0101

Gnomad4 OTH exome

AF:

0.0107

GnomAD4 genome

AF:

0.00818

AC:

1246

AN:

152246

Hom.:

Cov.:

AF XY:

0.00814

AC XY:

606

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00176

Gnomad4 AMR

AF:

0.00740

Gnomad4 ASJ

AF:

0.0144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.0175

Gnomad4 NFE

AF:

0.0118

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.0106

Hom.:

Bravo

AF:

0.00676

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.0106

EpiControl

AF:

0.00865

ClinVar

Significance: Benign

Submissions summary: Benign: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	Labcorp Genetics (formerly Invitae), Labcorp	Sep 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.2

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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