chr16-23836270-A-T

Variant names:

• chr16-23836270-A-T
• NM_002738.7:c.95A>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002738.7(PRKCB):​c.95A>T​(p.His32Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PRKCB NM_002738.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.47

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.756

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCB	NM_002738.7	c.95A>T	p.His32Leu	missense_variant	Exon 1 of 17	ENST00000643927.1	NP_002729.2
PRKCB	NM_212535.3	c.95A>T	p.His32Leu	missense_variant	Exon 1 of 17		NP_997700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCB	ENST00000643927.1	c.95A>T	p.His32Leu	missense_variant	Exon 1 of 17		NM_002738.7	ENSP00000496129.1
PRKCB	ENST00000321728.12	c.95A>T	p.His32Leu	missense_variant	Exon 1 of 17	1		ENSP00000318315.7
PRKCB	ENST00000498058.1	n.189A>T		non_coding_transcript_exon_variant	Exon 1 of 2	3
PRKCB	ENST00000645517.1	n.42A>T		non_coding_transcript_exon_variant	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.95A>T (p.H32L) alteration is located in exon 1 (coding exon 1) of the PRKCB gene. This alteration results from a A to T substitution at nucleotide position 95, causing the histidine (H) at amino acid position 32 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	25
DANN	Benign	0.91
DEOGEN2	Pathogenic	0.81	D;D;.;.
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Pathogenic	0.98	.;D;.;D
M_CAP	Pathogenic	0.77	D
MetaRNN	Pathogenic	0.76	D;D;D;D
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.0	M;M;M;M
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-4.2	.;D;.;D
REVEL	Uncertain	0.58
Sift	Uncertain	0.029	.;D;.;D
Sift4G	Uncertain	0.025	.;D;.;D
Polyphen		0.60	P;P;P;P
Vest4		0.63, 0.59
MutPred		0.47		Loss of disorder (P = 0.0522);Loss of disorder (P = 0.0522);Loss of disorder (P = 0.0522);Loss of disorder (P = 0.0522);
MVP		0.97
MPC		1.8
ClinPred		0.80	D
GERP RS		2.8
Varity_R		0.32
gMVP		0.99

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-23847591;