rs4364968

Variant names:

• chr10-6461769-C-A
• rs4364968
• NM_006257.5:c.1508+534G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006257.5(PRKCQ):​c.1508+534G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 151,956 control chromosomes in the GnomAD database, including 7,617 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 0.29 (7617 hom., cov: 32)
• Consequence: PRKCQ NM_006257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCQ	NM_006257.5	c.1508+534G>T		intron_variant	Intron 14 of 17	ENST00000263125.10	NP_006248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCQ	ENST00000263125.10	c.1508+534G>T		intron_variant	Intron 14 of 17	1	NM_006257.5	ENSP00000263125.5
PRKCQ	ENST00000397176.6	c.1508+534G>T		intron_variant	Intron 14 of 16	5		ENSP00000380361.2
PRKCQ	ENST00000539722.5	c.1133+534G>T		intron_variant	Intron 13 of 16	2		ENSP00000441752.1
ENSG00000302067	ENST00000783835.1	n.381+14797C>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44300 AN: 151838 Hom.: 7612 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.0672

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.292 AC: 44323 AN: 151956 Hom.: 7617 Cov.: 32 AF XY: 0.289 AC XY: 21441 AN XY: 74244

African (AFR) AF: 0.124 AC: 5146 AN: 41442

American (AMR) AF: 0.333 AC: 5079 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1282 AN: 3470

East Asian (EAS) AF: 0.0667 AC: 345 AN: 5170

South Asian (SAS) AF: 0.218 AC: 1051 AN: 4816

European-Finnish (FIN) AF: 0.399 AC: 4191 AN: 10504

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.385 AC: 26146 AN: 67966

Other (OTH) AF: 0.309 AC: 652 AN: 2112

Alfa AF: 0.345 Hom.: 19558

Bravo AF: 0.284

Asia WGS AF: 0.148 AC: 514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.33
DANN	Benign	0.66
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4364968; hg19: chr10-6503731;