NM_006257.5:c.661-103T>C

Variant names:

• chr10-6491915-A-G
• rs3815975
• NM_006257.5:c.661-103T>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.661-103T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,472,082 control chromosomes in the GnomAD database, including 124,701 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 0.45 (15655 hom., cov: 33)
  • Exomes 𝑓: 0.40 (109046 hom.)
• Consequence: PRKCQ NM_006257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327
• Publications: 9 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCQ	NM_006257.5	c.661-103T>C		intron_variant	Intron 7 of 17	ENST00000263125.10	NP_006248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCQ	ENST00000263125.10	c.661-103T>C		intron_variant	Intron 7 of 17	1	NM_006257.5	ENSP00000263125.5
PRKCQ	ENST00000397176.6	c.661-103T>C		intron_variant	Intron 7 of 16	5		ENSP00000380361.2
PRKCQ	ENST00000539722.5	c.286-103T>C		intron_variant	Intron 6 of 16	2		ENSP00000441752.1
ENSG00000302067	ENST00000783835.1	n.381+44943A>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67942 AN: 151972 Hom.: 15620 Cov.: 33

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.432

GnomAD4 exome AF: 0.403 AC: 532598 AN: 1319992 Hom.: 109046 AF XY: 0.401 AC XY: 263832 AN XY: 658184

African (AFR) AF: 0.551 AC: 16745 AN: 30366

American (AMR) AF: 0.461 AC: 19371 AN: 42004

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 8659 AN: 22906

East Asian (EAS) AF: 0.440 AC: 17068 AN: 38804

South Asian (SAS) AF: 0.321 AC: 24672 AN: 76944

European-Finnish (FIN) AF: 0.460 AC: 22923 AN: 49842

Middle Eastern (MID) AF: 0.380 AC: 2042 AN: 5380

European-Non Finnish (NFE) AF: 0.400 AC: 399049 AN: 998228

Other (OTH) AF: 0.398 AC: 22069 AN: 55518

GnomAD4 genome AF: 0.447 AC: 68025 AN: 152090 Hom.: 15655 Cov.: 33 AF XY: 0.446 AC XY: 33195 AN XY: 74360

African (AFR) AF: 0.544 AC: 22541 AN: 41470

American (AMR) AF: 0.420 AC: 6426 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1344 AN: 3466

East Asian (EAS) AF: 0.427 AC: 2214 AN: 5184

South Asian (SAS) AF: 0.325 AC: 1570 AN: 4828

European-Finnish (FIN) AF: 0.467 AC: 4936 AN: 10566

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.403 AC: 27398 AN: 67968

Other (OTH) AF: 0.437 AC: 923 AN: 2114

Alfa AF: 0.412 Hom.: 55878

Bravo AF: 0.452

Asia WGS AF: 0.436 AC: 1515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.73
PhyloP100		-0.33
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: rs3815975; hg19: chr10-6533877; COSMIC: COSV54118725;