rs3815975

Positions:

• chr10-6491915-A-G
• chr10-6491915-A-T

Variant summary

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

The NM_006257.5(PRKCQ):​c.661-103T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,472,082 control chromosomes in the GnomAD database, including 124,701 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 0.45 (15655 hom., cov: 33)
  • Exomes 𝑓: 0.40 (109046 hom.)
• Consequence: PRKCQ NM_006257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCQ	NM_006257.5	c.661-103T>C		intron_variant		ENST00000263125.10	NP_006248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCQ	ENST00000263125.10	c.661-103T>C		intron_variant		1	NM_006257.5	ENSP00000263125	P1
PRKCQ	ENST00000397176.6	c.661-103T>C		intron_variant		5		ENSP00000380361
PRKCQ	ENST00000539722.5	c.286-103T>C		intron_variant		2		ENSP00000441752

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67942 AN: 151972 Hom.: 15620 Cov.: 33

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.432

GnomAD4 exome AF: 0.403 AC: 532598 AN: 1319992 Hom.: 109046 AF XY: 0.401 AC XY: 263832 AN XY: 658184

Gnomad4 AFR exome AF: 0.551

Gnomad4 AMR exome AF: 0.461

Gnomad4 ASJ exome AF: 0.378

Gnomad4 EAS exome AF: 0.440

Gnomad4 SAS exome AF: 0.321

Gnomad4 FIN exome AF: 0.460

Gnomad4 NFE exome AF: 0.400

Gnomad4 OTH exome AF: 0.398

GnomAD4 genome AF: 0.447 AC: 68025 AN: 152090 Hom.: 15655 Cov.: 33 AF XY: 0.446 AC XY: 33195 AN XY: 74360

Gnomad4 AFR AF: 0.544

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.427

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.437

Alfa AF: 0.401 Hom.: 25030

Bravo AF: 0.452

Asia WGS AF: 0.436 AC: 1515 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	2.0
DANN	Benign	0.73

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: rs3815975; hg19: chr10-6533877; COSMIC: COSV54118725;