rs586457

Positions:

• chr10-6455460-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006257.5(PRKCQ):​c.1647+1214A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,148 control chromosomes in the GnomAD database, including 5,391 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 0.26 (5391 hom., cov: 32)
• Consequence: PRKCQ NM_006257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCQ	NM_006257.5	c.1647+1214A>G		intron_variant		ENST00000263125.10	NP_006248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCQ	ENST00000263125.10	c.1647+1214A>G		intron_variant		1	NM_006257.5	ENSP00000263125	P1
PRKCQ	ENST00000397176.6	c.1647+1214A>G		intron_variant		5		ENSP00000380361
PRKCQ	ENST00000539722.5	c.1272+1214A>G		intron_variant		2		ENSP00000441752

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39641 AN: 152030 Hom.: 5390 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.0735

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.254

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.261 AC: 39660 AN: 152148 Hom.: 5391 Cov.: 32 AF XY: 0.259 AC XY: 19235 AN XY: 74398

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.0727

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.252

Alfa AF: 0.279 Hom.: 12579

Bravo AF: 0.258

Asia WGS AF: 0.138 AC: 480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.71

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

LitVar

Other links and lift over

dbSNP: rs586457; hg19: chr10-6497422;