chr10-6566771-G-A

Variant names:

• chr10-6566771-G-A
• rs1887327
• NM_006257.5:c.-10+13440C>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.-10+13440C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 151,826 control chromosomes in the GnomAD database, including 42,333 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 0.71 (42333 hom., cov: 29)
• Consequence: PRKCQ NM_006257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.395
• Publications: 6 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 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.-10+13440C>T		intron	N/A	NP_006248.1
	PRKCQ	NM_001323265.1		c.-10+13730C>T		intron	N/A	NP_001310194.1
	PRKCQ	NM_001282644.2		c.-116+13440C>T		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.-10+13440C>T		intron	N/A	ENSP00000263125.5
	PRKCQ	ENST00000397176.6	TSL:5	c.-10+13440C>T		intron	N/A	ENSP00000380361.2
	PRKCQ	ENST00000539722.5	TSL:2	c.-324+13440C>T		intron	N/A	ENSP00000441752.1

Frequencies

GnomAD3 genomes AF: 0.712 AC: 108067 AN: 151708 Hom.: 42316 Cov.: 29

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.817

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.947

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.904

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.847

Gnomad OTH AF: 0.737

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

GnomAD4 genome AF: 0.712 AC: 108123 AN: 151826 Hom.: 42333 Cov.: 29 AF XY: 0.721 AC XY: 53496 AN XY: 74214

African (AFR) AF: 0.352 AC: 14527 AN: 41266

American (AMR) AF: 0.817 AC: 12487 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2601 AN: 3472

East Asian (EAS) AF: 0.947 AC: 4886 AN: 5158

South Asian (SAS) AF: 0.817 AC: 3913 AN: 4788

European-Finnish (FIN) AF: 0.904 AC: 9559 AN: 10578

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.847 AC: 57575 AN: 67976

Other (OTH) AF: 0.737 AC: 1553 AN: 2106

Alfa AF: 0.779 Hom.: 18224

Bravo AF: 0.688

Asia WGS AF: 0.833 AC: 2896 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.0
DANN	Benign	0.70
PhyloP100		0.40
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: rs1887327; hg19: chr10-6608733;