rs663532

Positions:

• chr10-6427794-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006257.5(PRKCQ):​c.*413A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0173 in 194,276 control chromosomes in the GnomAD database, including 48 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 0.019 (45 hom., cov: 33)
  • Exomes 𝑓: 0.012 (3 hom.)
• Consequence: PRKCQ NM_006257.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.811

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=-0.89).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0188 (2859/152294) while in subpopulation AFR AF= 0.0306 (1271/41554). AF 95% confidence interval is 0.0292. There are 45 homozygotes in gnomad4. There are 1432 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2859 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCQ	NM_006257.5	c.*413A>G		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.*413A>G		3_prime_UTR_variant	18/18	1	NM_006257.5	ENSP00000263125	P1
PRKCQ	ENST00000397176.6	c.*413A>G		3_prime_UTR_variant	17/17	5		ENSP00000380361
PRKCQ	ENST00000539722.5	c.*413A>G		3_prime_UTR_variant	17/17	2		ENSP00000441752

Frequencies

GnomAD3 genomes AF: 0.0188 AC: 2854 AN: 152176 Hom.: 44 Cov.: 33

Gnomad AFR AF: 0.0305

Gnomad AMI AF: 0.0582

Gnomad AMR AF: 0.00524

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.0242

Gnomad FIN AF: 0.0200

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0154

Gnomad OTH AF: 0.0125

GnomAD4 exome AF: 0.0119 AC: 498 AN: 41982 Hom.: 3 Cov.: 0 AF XY: 0.0118 AC XY: 259 AN XY: 21892

Gnomad4 AFR exome AF: 0.0326

Gnomad4 AMR exome AF: 0.00525

Gnomad4 ASJ exome AF: 0.00750

Gnomad4 EAS exome AF: 0.00429

Gnomad4 SAS exome AF: 0.0165

Gnomad4 FIN exome AF: 0.0137

Gnomad4 NFE exome AF: 0.0118

Gnomad4 OTH exome AF: 0.00907

GnomAD4 genome AF: 0.0188 AC: 2859 AN: 152294 Hom.: 45 Cov.: 33 AF XY: 0.0192 AC XY: 1432 AN XY: 74458

Gnomad4 AFR AF: 0.0306

Gnomad4 AMR AF: 0.00523

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.00386

Gnomad4 SAS AF: 0.0242

Gnomad4 FIN AF: 0.0200

Gnomad4 NFE AF: 0.0154

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.0225 Hom.: 3

Bravo AF: 0.0171

Asia WGS AF: 0.0190 AC: 65 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.47
DANN	Benign	0.34

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: rs663532; hg19: chr10-6469756;