10-6441898-C-G

Variant names:

• chr10-6441898-C-G
• rs1040506959
• NM_006257.5:c.1831G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006257.5(PRKCQ):​c.1831G>C​(p.Val611Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRKCQ NM_006257.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2721975).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCQ	NM_006257.5	c.1831G>C	p.Val611Leu	missense_variant	Exon 16 of 18	ENST00000263125.10	NP_006248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCQ	ENST00000263125.10	c.1831G>C	p.Val611Leu	missense_variant	Exon 16 of 18	1	NM_006257.5	ENSP00000263125.5
PRKCQ	ENST00000539722.5	c.1456G>C	p.Val486Leu	missense_variant	Exon 15 of 17	2		ENSP00000441752.1
PRKCQ	ENST00000397176.6	c.1648-10960G>C		intron_variant	Intron 15 of 16	5		ENSP00000380361.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0071	T;T;.
Eigen	Benign	-0.032
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.77	T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.070	.;N;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.73	.;N;N
REVEL	Benign	0.10
Sift	Uncertain	0.022	.;D;D
Sift4G	Uncertain	0.050	T;T;D
Polyphen		0.14	.;B;.
Vest4		0.30
MutPred		0.54		.;Loss of methylation at K612 (P = 0.041);.;
MVP		0.61
MPC		0.45
ClinPred		0.17	T
GERP RS		5.6
Varity_R		0.14
gMVP		0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs1040506959; hg19: chr10-6483860;