Genetic Variant NM_002738.7:c.995G>T (chr16-24123911-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G332A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

PRKCB
NM_002738.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.37

Publications

2 publications found

Variant links:

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]

PRKCB links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.995G>T	p.Gly332Val	missense	Exon 9 of 17	NP_002729.2
	PRKCB	NM_212535.3		c.995G>T	p.Gly332Val	missense	Exon 9 of 17	NP_997700.1	P05771-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRKCB	ENST00000643927.1	MANE Select	c.995G>T	p.Gly332Val	missense	Exon 9 of 17	ENSP00000496129.1	P05771-2
PRKCB	ENST00000321728.12	TSL:1	c.995G>T	p.Gly332Val	missense	Exon 9 of 17	ENSP00000318315.7	P05771-1
PRKCB	ENST00000965655.1		c.1073G>T	p.Gly358Val	missense	Exon 10 of 18	ENSP00000635714.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.39

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.052

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.5

PhyloP100

9.4

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.32

Sift

Benign

0.062

Sift4G

Benign

0.090

Polyphen

0.0010

Vest4

0.75

MutPred

0.27

Loss of loop (P = 0.0203)

MVP

0.93

MPC

1.3

ClinPred

0.95

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over