16-24123911-G-T

Variant names:

• chr16-24123911-G-T
• rs149128755
• NM_002738.7:c.995G>T

Variant summary

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

The NM_002738.7(PRKCB):​c.995G>T​(p.Gly332Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRKCB NM_002738.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.37

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCB	NM_002738.7	c.995G>T	p.Gly332Val	missense_variant	Exon 9 of 17	ENST00000643927.1	NP_002729.2
PRKCB	NM_212535.3	c.995G>T	p.Gly332Val	missense_variant	Exon 9 of 17		NP_997700.1
PRKCB	XM_047434365.1	c.608G>T	p.Gly203Val	missense_variant	Exon 8 of 16		XP_047290321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCB	ENST00000643927.1	c.995G>T	p.Gly332Val	missense_variant	Exon 9 of 17		NM_002738.7	ENSP00000496129.1
PRKCB	ENST00000321728.12	c.995G>T	p.Gly332Val	missense_variant	Exon 9 of 17	1		ENSP00000318315.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T;T;.;.
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	.;D;.;D
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.43	T;T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.5	M;M;M;M
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.4	.;N;.;N
REVEL	Uncertain	0.32
Sift	Benign	0.062	.;T;.;T
Sift4G	Benign	0.090	.;T;.;T
Polyphen		0.0010	B;B;B;B
Vest4		0.75, 0.80
MutPred		0.27		Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);
MVP		0.93
MPC		1.3
ClinPred		0.95	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.75

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: rs149128755; hg19: chr16-24135232;