16-23836337-C-T

Variant names:

• chr16-23836337-C-T
• rs115667450
• NM_002738.7:c.162C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_002738.7(PRKCB):​c.162C>T​(p.Thr54Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00024 in 1,602,246 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: PRKCB NM_002738.7 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.79
• Publications: 1 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).
• BP6: Variant 16-23836337-C-T is Benign according to our data. Variant chr16-23836337-C-T is described in ClinVar as Benign. ClinVar VariationId is 744416.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.79 with no splicing effect.
• BS2: High AC in GnomAd4 at 186 AD gene.

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.162C>T	p.Thr54Thr	synonymous	Exon 1 of 17	NP_002729.2
	PRKCB	NM_212535.3		c.162C>T	p.Thr54Thr	synonymous	Exon 1 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.162C>T	p.Thr54Thr	synonymous	Exon 1 of 17	ENSP00000496129.1	P05771-2
	PRKCB	ENST00000321728.12	TSL:1	c.162C>T	p.Thr54Thr	synonymous	Exon 1 of 17	ENSP00000318315.7	P05771-1
	PRKCB	ENST00000965655.1		c.162C>T	p.Thr54Thr	synonymous	Exon 1 of 18	ENSP00000635714.1

Frequencies

GnomAD3 genomes AF: 0.00122 AC: 185 AN: 152016 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00435

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

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: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000248 AC: 59 AN: 238072 AF XY: 0.000147

Gnomad AFR exome AF: 0.00378

Gnomad AMR exome AF: 0.000236

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000137 AC: 199 AN: 1450122 Hom.: 0 Cov.: 33 AF XY: 0.000125 AC XY: 90 AN XY: 721698

African (AFR) AF: 0.00536 AC: 167 AN: 31130

American (AMR) AF: 0.000248 AC: 11 AN: 44310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25682

East Asian (EAS) AF: 0.00 AC: 0 AN: 38110

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.000418 AC: 2 AN: 4784

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107140

Other (OTH) AF: 0.000284 AC: 17 AN: 59776

GnomAD4 genome AF: 0.00122 AC: 186 AN: 152124 Hom.: 1 Cov.: 33 AF XY: 0.00134 AC XY: 100 AN XY: 74374

African (AFR) AF: 0.00436 AC: 181 AN: 41536

American (AMR) AF: 0.000196 AC: 3 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5126

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67946

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000395 Hom.: 0

Bravo AF: 0.00144

Asia WGS AF: 0.000289 AC: 1 AN: 3470

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	15
DANN	Uncertain	0.98
PhyloP100		1.8
PromoterAI		-0.027	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Mutation Taster		=100/0	polymorphism

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: rs115667450; hg19: chr16-23847658;