rs11259272

Positions:

• chr10-6504109-A-G

Variant summary

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

The NM_006257.5(PRKCQ):​c.379+3327T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 152,122 control chromosomes in the GnomAD database, including 15,908 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 0.42 (15908 hom., cov: 32)
• Consequence: PRKCQ NM_006257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCQ	NM_006257.5	c.379+3327T>C		intron_variant		ENST00000263125.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCQ	ENST00000263125.10	c.379+3327T>C		intron_variant		1	NM_006257.5	P1
PRKCQ	ENST00000397176.6	c.379+3327T>C		intron_variant		5
PRKCQ	ENST00000539722.5	c.5-5551T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63271 AN: 152002 Hom.: 15902 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.416 AC: 63275 AN: 152122 Hom.: 15908 Cov.: 32 AF XY: 0.416 AC XY: 30946 AN XY: 74364

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.402

Gnomad4 FIN AF: 0.499

Gnomad4 NFE AF: 0.538

Gnomad4 OTH AF: 0.450

Alfa AF: 0.501 Hom.: 9932

Bravo AF: 0.412

Asia WGS AF: 0.382 AC: 1331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.15
DANN	Benign	0.66

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: rs11259272; hg19: chr10-6546071;