rs542817

Variant names:

• chr10-6462714-A-G
• rs542817
• NM_006257.5:c.1446-349T>C

Variant summary

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

The NM_006257.5(PRKCQ):​c.1446-349T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,172 control chromosomes in the GnomAD database, including 1,445 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 0.13 (1445 hom., cov: 32)
• Consequence: PRKCQ NM_006257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240
• Publications: 2 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 (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006257.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCQ	NM_006257.5	MANE Select	c.1446-349T>C		intron	N/A	NP_006248.1
	PRKCQ	NM_001323265.1		c.1446-349T>C		intron	N/A	NP_001310194.1
	PRKCQ	NM_001282644.2		c.1338-349T>C		intron	N/A	NP_001269573.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCQ	ENST00000263125.10	TSL:1 MANE Select	c.1446-349T>C		intron	N/A	ENSP00000263125.5
	PRKCQ	ENST00000397176.6	TSL:5	c.1446-349T>C		intron	N/A	ENSP00000380361.2
	PRKCQ	ENST00000539722.5	TSL:2	c.1071-349T>C		intron	N/A	ENSP00000441752.1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19052 AN: 152054 Hom.: 1441 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.0791

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.0799

Gnomad SAS AF: 0.0764

Gnomad FIN AF: 0.0540

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.0998

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.125 AC: 19086 AN: 152172 Hom.: 1445 Cov.: 32 AF XY: 0.122 AC XY: 9053 AN XY: 74416

African (AFR) AF: 0.212 AC: 8812 AN: 41496

American (AMR) AF: 0.0790 AC: 1208 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 468 AN: 3470

East Asian (EAS) AF: 0.0788 AC: 408 AN: 5180

South Asian (SAS) AF: 0.0773 AC: 373 AN: 4826

European-Finnish (FIN) AF: 0.0540 AC: 572 AN: 10602

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.0998 AC: 6786 AN: 67984

Other (OTH) AF: 0.118 AC: 250 AN: 2116

Alfa AF: 0.110 Hom.: 1021

Bravo AF: 0.130

Asia WGS AF: 0.0850 AC: 296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.48
PhyloP100		-0.024
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs542817; hg19: chr10-6504676;