rs11259272

Variant names:

• chr10-6504109-A-G
• rs11259272
• NM_006257.5:c.379+3327T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

ENSG00000302067 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PRKCQ	NM_006257.5	c.379+3327T>C		intron_variant	Intron 4 of 17	ENST00000263125.10	NP_006248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCQ	ENST00000263125.10	c.379+3327T>C		intron_variant	Intron 4 of 17	1	NM_006257.5	ENSP00000263125.5
PRKCQ	ENST00000397176.6	c.379+3327T>C		intron_variant	Intron 4 of 16	5		ENSP00000380361.2
PRKCQ	ENST00000539722.5	c.5-5551T>C		intron_variant	Intron 3 of 16	2		ENSP00000441752.1
ENSG00000302067	ENST00000783835.1	n.382-33304A>G		intron_variant	Intron 2 of 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

African (AFR) AF: 0.116 AC: 4820 AN: 41532

American (AMR) AF: 0.586 AC: 8958 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1551 AN: 3470

East Asian (EAS) AF: 0.486 AC: 2511 AN: 5170

South Asian (SAS) AF: 0.402 AC: 1939 AN: 4824

European-Finnish (FIN) AF: 0.499 AC: 5272 AN: 10564

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.538 AC: 36542 AN: 67968

Other (OTH) AF: 0.450 AC: 949 AN: 2110

Alfa AF: 0.502 Hom.: 10995

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
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11259272; hg19: chr10-6546071;