chr10-6514592-C-T

Position:

• chr10-6514592-C-T

Variant summary

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

The ENST00000263125.10(PRKCQ):​c.118+426G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 152,192 control chromosomes in the GnomAD database, including 43,178 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 0.75 (43178 hom., cov: 33)
• Consequence: PRKCQ ENST00000263125.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCQ	NM_006257.5	c.118+426G>A		intron_variant		ENST00000263125.10	NP_006248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCQ	ENST00000263125.10	c.118+426G>A		intron_variant		1	NM_006257.5	ENSP00000263125	P1
PRKCQ	ENST00000397176.6	c.118+426G>A		intron_variant		5		ENSP00000380361
PRKCQ	ENST00000539722.5	c.-197+426G>A		intron_variant		2		ENSP00000441752

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113601 AN: 152074 Hom.: 43147 Cov.: 33

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.859

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.764

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

GnomAD4 genome AF: 0.747 AC: 113682 AN: 152192 Hom.: 43178 Cov.: 33 AF XY: 0.747 AC XY: 55539 AN XY: 74396

Gnomad4 AFR AF: 0.605

Gnomad4 AMR AF: 0.847

Gnomad4 ASJ AF: 0.781

Gnomad4 EAS AF: 0.662

Gnomad4 SAS AF: 0.728

Gnomad4 FIN AF: 0.796

Gnomad4 NFE AF: 0.807

Gnomad4 OTH AF: 0.758

Alfa AF: 0.800 Hom.: 99022

Bravo AF: 0.743

Asia WGS AF: 0.670 AC: 2332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.16
DANN	Benign	0.65

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: rs571715; hg19: chr10-6556554;