16-24092867-C-T

Variant names:

• chr16-24092867-C-T
• rs3729896
• NM_002738.7:c.606C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_002738.7(PRKCB):​c.606C>T​(p.Pro202Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0401 in 1,614,006 control chromosomes in the GnomAD database, including 1,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.036 (131 hom., cov: 32)
  • Exomes 𝑓: 0.040 (1359 hom.)
• Consequence: PRKCB NM_002738.7 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.17
• Publications: 16 publications found

Genes affected

PRKCB (HGNC:9395): (protein kinase C beta) Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and 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 in cells. The protein encoded by this gene is one of the PKC family members. This protein kinase has been reported to be involved in many different cellular functions, such as B cell activation, apoptosis induction, endothelial cell proliferation, and intestinal sugar absorption. Studies in mice also suggest that this kinase may also regulate neuronal functions and correlate fear-induced conflict behavior after stress. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 16-24092867-C-T is Benign according to our data. Variant chr16-24092867-C-T is described in ClinVar as Benign. ClinVar VariationId is 3055721.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-2.17 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002738.7. 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
	PRKCB	NM_002738.7	MANE Select	c.606C>T	p.Pro202Pro	synonymous	Exon 6 of 17	NP_002729.2
	PRKCB	NM_212535.3		c.606C>T	p.Pro202Pro	synonymous	Exon 6 of 17	NP_997700.1	P05771-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCB	ENST00000643927.1	MANE Select	c.606C>T	p.Pro202Pro	synonymous	Exon 6 of 17	ENSP00000496129.1	P05771-2
	PRKCB	ENST00000321728.12	TSL:1	c.606C>T	p.Pro202Pro	synonymous	Exon 6 of 17	ENSP00000318315.7	P05771-1
	PRKCB	ENST00000965655.1		c.684C>T	p.Pro228Pro	synonymous	Exon 7 of 18	ENSP00000635714.1

Frequencies

GnomAD3 genomes AF: 0.0365 AC: 5546 AN: 152110 Hom.: 132 Cov.: 32

Gnomad AFR AF: 0.0268

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0185

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.0622

Gnomad FIN AF: 0.0427

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0375

Gnomad OTH AF: 0.0330

GnomAD2 exomes AF: 0.0418 AC: 10507 AN: 251374 AF XY: 0.0420

Gnomad AFR exome AF: 0.0255

Gnomad AMR exome AF: 0.0159

Gnomad ASJ exome AF: 0.0296

Gnomad EAS exome AF: 0.117

Gnomad FIN exome AF: 0.0436

Gnomad NFE exome AF: 0.0380

Gnomad OTH exome AF: 0.0384

GnomAD4 exome AF: 0.0405 AC: 59174 AN: 1461778 Hom.: 1359 Cov.: 31 AF XY: 0.0405 AC XY: 29445 AN XY: 727194

African (AFR) AF: 0.0260 AC: 870 AN: 33478

American (AMR) AF: 0.0170 AC: 759 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0295 AC: 771 AN: 26132

East Asian (EAS) AF: 0.0874 AC: 3468 AN: 39688

South Asian (SAS) AF: 0.0520 AC: 4482 AN: 86228

European-Finnish (FIN) AF: 0.0456 AC: 2433 AN: 53398

Middle Eastern (MID) AF: 0.0231 AC: 133 AN: 5768

European-Non Finnish (NFE) AF: 0.0393 AC: 43706 AN: 1111972

Other (OTH) AF: 0.0423 AC: 2552 AN: 60392

GnomAD4 genome AF: 0.0364 AC: 5543 AN: 152228 Hom.: 131 Cov.: 32 AF XY: 0.0365 AC XY: 2718 AN XY: 74414

African (AFR) AF: 0.0267 AC: 1108 AN: 41540

American (AMR) AF: 0.0184 AC: 282 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0271 AC: 94 AN: 3470

East Asian (EAS) AF: 0.114 AC: 588 AN: 5172

South Asian (SAS) AF: 0.0620 AC: 299 AN: 4820

European-Finnish (FIN) AF: 0.0427 AC: 452 AN: 10584

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0375 AC: 2554 AN: 68026

Other (OTH) AF: 0.0326 AC: 69 AN: 2114

Alfa AF: 0.0362 Hom.: 123

Bravo AF: 0.0350

Asia WGS AF: 0.0780 AC: 271 AN: 3478

EpiCase AF: 0.0364

EpiControl AF: 0.0360

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PRKCB-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	11
DANN	Benign	0.59
PhyloP100		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	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: rs3729896; hg19: chr16-24104188; COSMIC: COSV57781608; COSMIC: COSV57781608;