10-6497055-T-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2 BP4_Strong BP6_Moderate BS2

The NM_006257.5(PRKCQ):c.640A>G(p.Ile214Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000693 in 1,613,110 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00039 (4 hom.)
• Consequence: PRKCQ NM_006257.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.775

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 Benign. Variant got -9 ACMG points.

• PP2: Missense variant where missense usually causes diseases, PRKCQ
• BP4: Computational evidence support a benign effect (MetaRNN=0.0076305866).
• BP6: Variant 10-6497055-T-C is Benign according to our data. Variant chr10-6497055-T-C is described in ClinVar as [Benign]. Clinvar id is 727330.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 551 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCQ	NM_006257.5	c.640A>G	p.Ile214Val	missense_variant	7/18	ENST00000263125.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCQ	ENST00000263125.10	c.640A>G	p.Ile214Val	missense_variant	7/18	1	NM_006257.5	P1
PRKCQ	ENST00000397176.6	c.640A>G	p.Ile214Val	missense_variant	7/17	5
PRKCQ	ENST00000539722.5	c.265A>G	p.Ile89Val	missense_variant	6/17	2

Frequencies

GnomAD3 genomes AF: 0.00362 AC: 551 AN: 152246 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00107 AC: 268 AN: 251100 Hom.: 1 AF XY: 0.000774 AC XY: 105 AN XY: 135690

Gnomad AFR exome AF: 0.0138

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000388 AC: 567 AN: 1460746 Hom.: 4 Cov.: 32 AF XY: 0.000314 AC XY: 228 AN XY: 726680

Gnomad4 AFR exome AF: 0.0135

Gnomad4 AMR exome AF: 0.00103

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000809

Gnomad4 OTH exome AF: 0.000863

GnomAD4 genome AF: 0.00362 AC: 551 AN: 152364 Hom.: 3 Cov.: 32 AF XY: 0.00327 AC XY: 244 AN XY: 74510

Gnomad4 AFR AF: 0.0127

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000676 Hom.: 0

Bravo AF: 0.00438

ESP6500AA AF: 0.0125 AC: 55

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00129 AC: 157

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	0.10
Dann	Benign	0.22
DEOGEN2	Benign	0.0033	T;T;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.75	T;T;T;T
MetaRNN	Benign	0.0076	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.40	T
Sift4G	Benign	0.31	T;T;T;T
Polyphen		0.0	.;B;B;.
Vest4		0.16
MVP		0.31
MPC		0.38
ClinPred		0.013	T
GERP RS		-4.5
Varity_R		0.019
gMVP		0.097

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: rs148789784; hg19: chr10-6539017;