chr10-6427711-C-T

Position:

• chr10-6427711-C-T

Variant summary

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

The NM_006257.5(PRKCQ):​c.*496G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 155,088 control chromosomes in the GnomAD database, including 3,267 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 0.18 (3188 hom., cov: 32)
  • Exomes 𝑓: 0.21 (79 hom.)
• Consequence: PRKCQ NM_006257.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.528

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 (NFE) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCQ	NM_006257.5	c.*496G>A		3_prime_UTR_variant	18/18	ENST00000263125.10	NP_006248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCQ	ENST00000263125.10	c.*496G>A		3_prime_UTR_variant	18/18	1	NM_006257.5	ENSP00000263125	P1
PRKCQ	ENST00000397176.6	c.*496G>A		3_prime_UTR_variant	17/17	5		ENSP00000380361
PRKCQ	ENST00000539722.5	c.*496G>A		3_prime_UTR_variant	17/17	2		ENSP00000441752

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27405 AN: 152052 Hom.: 3184 Cov.: 32

Gnomad AFR AF: 0.0448

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.0688

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.184

GnomAD4 exome AF: 0.209 AC: 611 AN: 2918 Hom.: 79 Cov.: 0 AF XY: 0.190 AC XY: 292 AN XY: 1534

Gnomad4 AFR exome AF: 0.0714

Gnomad4 AMR exome AF: 0.247

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.0833

Gnomad4 SAS exome AF: 0.113

Gnomad4 FIN exome AF: 0.208

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.220

GnomAD4 genome AF: 0.180 AC: 27411 AN: 152170 Hom.: 3188 Cov.: 32 AF XY: 0.181 AC XY: 13485 AN XY: 74394

Gnomad4 AFR AF: 0.0447

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.0684

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.183

Alfa AF: 0.228 Hom.: 5692

Bravo AF: 0.172

Asia WGS AF: 0.109 AC: 378 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	3.3
DANN	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2453; hg19: chr10-6469673;