rs764851728

Variant names:

• chr10-6441955-G-A
• rs764851728
• NM_006257.5:c.1774C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-6441955-G-A
• chr10-6441955-G-C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 3P and 4B. PM2 PP3 BS2

The NM_006257.5(PRKCQ):​c.1774C>T​(p.Arg592Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,794 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R592G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: PRKCQ NM_006257.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.87
• Publications: 3 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.834
• BS2: High AC in GnomAdExome4 at 5 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCQ	NM_006257.5	MANE Select	c.1774C>T	p.Arg592Cys	missense	Exon 16 of 18	NP_006248.1	Q04759-1
	PRKCQ	NM_001323265.1		c.1774C>T	p.Arg592Cys	missense	Exon 16 of 18	NP_001310194.1	Q04759-1
	PRKCQ	NM_001282644.2		c.1666C>T	p.Arg556Cys	missense	Exon 16 of 18	NP_001269573.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCQ	ENST00000263125.10	TSL:1 MANE Select	c.1774C>T	p.Arg592Cys	missense	Exon 16 of 18	ENSP00000263125.5	Q04759-1
	PRKCQ	ENST00000915286.1		c.1774C>T	p.Arg592Cys	missense	Exon 16 of 18	ENSP00000585345.1
	PRKCQ	ENST00000866196.1		c.1774C>T	p.Arg592Cys	missense	Exon 16 of 18	ENSP00000536255.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461794 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727202

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5754

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111958

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.010	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.032	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	1.3	L
PhyloP100		7.9
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	0.49	N
REVEL	Uncertain	0.43
Sift	Benign	0.099	T
Sift4G	Benign	0.20	T
Polyphen		1.0	D
Vest4		0.89
MutPred		0.64		Loss of disorder (P = 0.0408)
MVP		0.82
MPC		0.64
ClinPred		0.92	D
GERP RS		5.6
Varity_R		0.37
gMVP		0.82
Mutation Taster		=7/93	disease causing

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: rs764851728; hg19: chr10-6483917; COSMIC: COSV107312965;