10-6428225-C-T

Variant names:

• chr10-6428225-C-T
• NM_006257.5:c.2103G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006257.5(PRKCQ):​c.2103G>A​(p.Met701Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRKCQ NM_006257.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.36
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.2103G>A	p.Met701Ile	missense	Exon 18 of 18	NP_006248.1	Q04759-1
	PRKCQ	NM_001323265.1		c.2103G>A	p.Met701Ile	missense	Exon 18 of 18	NP_001310194.1	Q04759-1
	PRKCQ	NM_001282644.2		c.1995G>A	p.Met665Ile	missense	Exon 18 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.2103G>A	p.Met701Ile	missense	Exon 18 of 18	ENSP00000263125.5	Q04759-1
	PRKCQ	ENST00000915286.1		c.2127G>A	p.Met709Ile	missense	Exon 18 of 18	ENSP00000585345.1
	PRKCQ	ENST00000866196.1		c.2103G>A	p.Met701Ile	missense	Exon 18 of 18	ENSP00000536255.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.024	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.2	L
PhyloP100		7.4
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.23
Sift	Benign	0.14	T
Sift4G	Benign	0.25	T
Polyphen		0.94	P
Vest4		0.56
MutPred		0.34		Loss of disorder (P = 0.0238)
MVP		0.55
MPC		0.65
ClinPred		0.83	D
GERP RS		5.6
Varity_R		0.60
gMVP		0.77
Mutation Taster		=46/54	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

hg19: chr10-6470187;