NM_006257.5:c.1846C>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_006257.5(PRKCQ):​c.1846C>A​(p.Arg616Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,613,574 control chromosomes in the GnomAD database, including 36,221 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (2742 hom., cov: 32)
  • Exomes 𝑓: 0.21 (33479 hom.)
• Consequence: PRKCQ NM_006257.5 synonymous
• 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP7: Synonymous conserved (PhyloP=1.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCQ	NM_006257.5	c.1846C>A	p.Arg616Arg	synonymous_variant	Exon 17 of 18	ENST00000263125.10	NP_006248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCQ	ENST00000263125.10	c.1846C>A	p.Arg616Arg	synonymous_variant	Exon 17 of 18	1	NM_006257.5	ENSP00000263125.5

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27775 AN: 152016 Hom.: 2739 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.0327

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.171

GnomAD2 exomes AF: 0.174 AC: 43605 AN: 250646 AF XY: 0.178

Gnomad AFR exome AF: 0.146

Gnomad AMR exome AF: 0.0825

Gnomad ASJ exome AF: 0.153

Gnomad EAS exome AF: 0.0350

Gnomad FIN exome AF: 0.254

Gnomad NFE exome AF: 0.223

Gnomad OTH exome AF: 0.186

GnomAD4 exome AF: 0.207 AC: 302011 AN: 1461440 Hom.: 33479 Cov.: 33 AF XY: 0.205 AC XY: 148819 AN XY: 727024

African (AFR) AF: 0.146 AC: 4888 AN: 33474

American (AMR) AF: 0.0867 AC: 3875 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 4198 AN: 26130

East Asian (EAS) AF: 0.0202 AC: 803 AN: 39692

South Asian (SAS) AF: 0.142 AC: 12211 AN: 86230

European-Finnish (FIN) AF: 0.258 AC: 13781 AN: 53320

Middle Eastern (MID) AF: 0.105 AC: 607 AN: 5766

European-Non Finnish (NFE) AF: 0.225 AC: 249803 AN: 1111742

Other (OTH) AF: 0.196 AC: 11845 AN: 60378

GnomAD4 genome AF: 0.183 AC: 27777 AN: 152134 Hom.: 2742 Cov.: 32 AF XY: 0.181 AC XY: 13445 AN XY: 74386

African (AFR) AF: 0.143 AC: 5930 AN: 41496

American (AMR) AF: 0.134 AC: 2042 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 563 AN: 3470

East Asian (EAS) AF: 0.0330 AC: 171 AN: 5180

South Asian (SAS) AF: 0.144 AC: 694 AN: 4824

European-Finnish (FIN) AF: 0.249 AC: 2641 AN: 10598

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15225 AN: 67966

Other (OTH) AF: 0.168 AC: 354 AN: 2110

Alfa AF: 0.197 Hom.: 12770

Bravo AF: 0.172

Asia WGS AF: 0.0830 AC: 291 AN: 3478

EpiCase AF: 0.207

EpiControl AF: 0.206

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	7.5
DANN	Benign	0.59
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs11258747; hg19: chr10-6472891; COSMIC: COSV54107502;