chr10-6430929-G-C

Variant names:

• chr10-6430929-G-C
• rs11258747
• NM_006257.5:c.1846C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 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
• Publications: 58 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.853

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.1846C>G	p.Arg616Gly	missense	Exon 17 of 18	NP_006248.1
	PRKCQ	NM_001323265.1		c.1846C>G	p.Arg616Gly	missense	Exon 17 of 18	NP_001310194.1
	PRKCQ	NM_001282644.2		c.1738C>G	p.Arg580Gly	missense	Exon 17 of 18	NP_001269573.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCQ	ENST00000263125.10	TSL:1 MANE Select	c.1846C>G	p.Arg616Gly	missense	Exon 17 of 18	ENSP00000263125.5
	PRKCQ	ENST00000397176.6	TSL:5	c.1657C>G	p.Arg553Gly	missense	Exon 16 of 17	ENSP00000380361.2
	PRKCQ	ENST00000539722.5	TSL:2	c.1471C>G	p.Arg491Gly	missense	Exon 16 of 17	ENSP00000441752.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250646 AF XY: 0.00

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 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

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111866

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

Alfa AF: 0.00000163 Hom.: 12770

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Benign	0.062	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.1
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	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
Mutation Taster		=17/83	disease causing

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

Other links and lift over

dbSNP: rs11258747; hg19: chr10-6472891;