10-6530263-C-T

Variant names:

• chr10-6530263-C-T
• rs11259403
• NM_006257.5:c.-9-15119G>A

Variant summary

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

The NM_006257.5(PRKCQ):​c.-9-15119G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 151,972 control chromosomes in the GnomAD database, including 23,908 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 0.51 (23908 hom., cov: 31)
• Consequence: PRKCQ NM_006257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.782

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 (AMR) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCQ	NM_006257.5	c.-9-15119G>A		intron_variant	Intron 1 of 17	ENST00000263125.10	NP_006248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCQ	ENST00000263125.10	c.-9-15119G>A		intron_variant	Intron 1 of 17	1	NM_006257.5	ENSP00000263125.5
PRKCQ	ENST00000397176.6	c.-9-15119G>A		intron_variant	Intron 1 of 16	5		ENSP00000380361.2
PRKCQ	ENST00000539722.5	c.-323-15119G>A		intron_variant	Intron 1 of 16	2		ENSP00000441752.1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77194 AN: 151854 Hom.: 23894 Cov.: 31

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.508 AC: 77218 AN: 151972 Hom.: 23908 Cov.: 31 AF XY: 0.512 AC XY: 38045 AN XY: 74278

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.665

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.658

Gnomad4 NFE AF: 0.665

Gnomad4 OTH AF: 0.569

Alfa AF: 0.646 Hom.: 73081

Bravo AF: 0.490

Asia WGS AF: 0.516 AC: 1797 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	0.30
DANN	Benign	0.69

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: rs11259403; hg19: chr10-6572225;