10-6430929-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP2 PP3_Moderate

The NM_006257.5(PRKCQ):c.1846C>G(p.Arg616Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PRKCQ NM_006257.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

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

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, PRKCQ
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.853

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCQ	NM_006257.5	c.1846C>G	p.Arg616Gly	missense_variant	17/18	ENST00000263125.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCQ	ENST00000263125.10	c.1846C>G	p.Arg616Gly	missense_variant	17/18	1	NM_006257.5	P1
PRKCQ	ENST00000397176.6	c.1657C>G	p.Arg553Gly	missense_variant	16/17	5
PRKCQ	ENST00000539722.5	c.1471C>G	p.Arg491Gly	missense_variant	16/17	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250646 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135472

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461630 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727120

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.00000344 Hom.: 5988

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
Cadd	Uncertain	24
Dann	Benign	0.94
DEOGEN2	Benign	0.12	T;T;.;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Pathogenic	1.0	D;D;D;D
M_CAP	Benign	0.062	D
MetaRNN	Pathogenic	0.85	D;D;D;D
MetaSVM	Benign	-0.33	T
MutationTaster	Benign	0.0000019	P;P;P
PrimateAI	Uncertain	0.72	T
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		1.0, 1.0	.;D;D;.
Vest4		0.91
MutPred		0.72		.;Loss of MoRF binding (P = 0.0181);.;.;
MVP		0.78
MPC		1.5
ClinPred		0.98	D
GERP RS		1.6
Varity_R		0.91
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11258747; hg19: chr10-6472891;