rs4748153

Variant names:

• chr10-6564579-C-T
• rs4748153
• NM_006257.5:c.-10+15632G>A

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+15632G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,096 control chromosomes in the GnomAD database, including 845 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 0.10 (845 hom., cov: 32)
• Consequence: PRKCQ NM_006257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680
• Publications: 11 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCQ	NM_006257.5	c.-10+15632G>A		intron_variant	Intron 1 of 17	ENST00000263125.10	NP_006248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCQ	ENST00000263125.10	c.-10+15632G>A		intron_variant	Intron 1 of 17	1	NM_006257.5	ENSP00000263125.5
PRKCQ	ENST00000397176.6	c.-10+15632G>A		intron_variant	Intron 1 of 16	5		ENSP00000380361.2
PRKCQ	ENST00000539722.5	c.-324+15632G>A		intron_variant	Intron 1 of 16	2		ENSP00000441752.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15367 AN: 151978 Hom.: 844 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0818

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.00637

Gnomad SAS AF: 0.0785

Gnomad FIN AF: 0.0623

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.101 AC: 15381 AN: 152096 Hom.: 845 Cov.: 32 AF XY: 0.0972 AC XY: 7223 AN XY: 74348

African (AFR) AF: 0.107 AC: 4454 AN: 41454

American (AMR) AF: 0.0817 AC: 1249 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 515 AN: 3470

East Asian (EAS) AF: 0.00639 AC: 33 AN: 5166

South Asian (SAS) AF: 0.0792 AC: 381 AN: 4812

European-Finnish (FIN) AF: 0.0623 AC: 661 AN: 10610

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7694 AN: 67970

Other (OTH) AF: 0.111 AC: 235 AN: 2114

Alfa AF: 0.111 Hom.: 4289

Bravo AF: 0.103

Asia WGS AF: 0.0640 AC: 222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.5
DANN	Benign	0.70
PhyloP100		0.068
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: rs4748153; hg19: chr10-6606541;