Genetic Variant PRKCQ:c.*496G>A (chr10-6427711-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_006257.5(PRKCQ):c.*496G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 155,088 control chromosomes in the GnomAD database, including 3,267 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 0.18 ( 3188 hom., cov: 32)

Exomes 𝑓: 0.21 ( 79 hom. )

Consequence

PRKCQ
NM_006257.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.528

Publications

11 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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCQ	NM_006257.5 link	c.*496G>A		3_prime_UTR_variant	Exon 18 of 18	ENST00000263125.10	NP_006248.1	Q04759-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCQ	ENST00000263125.10 link	c.*496G>A		3_prime_UTR_variant	Exon 18 of 18	1	NM_006257.5	ENSP00000263125.5		Q04759-1

Frequencies

GnomAD3 genomes

AF:

0.180

AC:

27405

AN:

152052

Hom.:

3184

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0448

Gnomad AMI

AF:

0.111

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.207

Gnomad EAS

AF:

0.0688

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.318

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.244

Gnomad OTH

AF:

0.184

GnomAD4 exome

AF:

0.209

AC:

611

AN:

2918

Hom.:

Cov.:

AF XY:

0.190

AC XY:

292

AN XY:

1534

show subpopulations

African (AFR)

AF:

0.0714

AC:

AN:

American (AMR)

AF:

0.247

AC:

157

AN:

636

Ashkenazi Jewish (ASJ)

AF:

0.143

AC:

AN:

East Asian (EAS)

AF:

0.0833

AC:

AN:

South Asian (SAS)

AF:

0.113

AC:

AN:

328

European-Finnish (FIN)

AF:

0.208

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.217

AC:

376

AN:

1732

Other (OTH)

AF:

0.220

AC:

AN:

132

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.180

AC:

27411

AN:

152170

Hom.:

3188

Cov.:

AF XY:

0.181

AC XY:

13485

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.0447

AC:

1857

AN:

41532

American (AMR)

AF:

0.221

AC:

3385

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.207

AC:

719

AN:

3466

East Asian (EAS)

AF:

0.0684

AC:

354

AN:

5178

South Asian (SAS)

AF:

0.124

AC:

599

AN:

4824

European-Finnish (FIN)

AF:

0.318

AC:

3360

AN:

10580

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.244

AC:

16579

AN:

67980

Other (OTH)

AF:

0.183

AC:

386

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1096

2191

3287

4382

5478

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

290

580

870

1160

1450

<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:

0.223

Hom.:

6951

Bravo

AF:

0.172

Asia WGS

AF:

0.109

AC:

378

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.3

(source)

DANN

Benign

0.55

PhyloP100

0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

Computational scores

Splicing

Publications

Other links and lift over