10-6430853-T-G

Position:

• chr10-6430853-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006257.5(PRKCQ):​c.1922A>C​(p.Glu641Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PRKCQ NM_006257.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.27

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.078832686).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCQ	NM_006257.5	c.1922A>C	p.Glu641Ala	missense_variant	17/18	ENST00000263125.10	NP_006248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCQ	ENST00000263125.10	c.1922A>C	p.Glu641Ala	missense_variant	17/18	1	NM_006257.5	ENSP00000263125.5
PRKCQ	ENST00000397176.6	c.1733A>C	p.Glu578Ala	missense_variant	16/17	5		ENSP00000380361.2
PRKCQ	ENST00000539722.5	c.1547A>C	p.Glu516Ala	missense_variant	16/17	2		ENSP00000441752.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461872 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2024

The c.1922A>C (p.E641A) alteration is located in exon 1 (coding exon 1) of the PRKCQ gene. This alteration results from a A to C substitution at nucleotide position 1922, causing the glutamic acid (E) at amino acid position 641 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	19
DANN	Benign	0.88
DEOGEN2	Benign	0.0023	T;T;.;.
Eigen	Benign	-0.14
Eigen_PC	Benign	0.023
FATHMM_MKL	Benign	0.40	N
LIST_S2	Uncertain	0.89	D;D;D;D
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.079	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.7	.;N;.;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.10	.;N;N;N
REVEL	Benign	0.084
Sift	Benign	0.88	.;T;T;T
Sift4G	Benign	0.83	T;T;T;T
Polyphen		0.0	.;B;B;.
Vest4		0.093
MutPred		0.33		.;Loss of disorder (P = 0.0236);.;.;
MVP		0.45
MPC		0.49
ClinPred		0.16	T
GERP RS		3.8
Varity_R		0.091
gMVP		0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-6472815;