chr16-24154795-G-T
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Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PP2PP3_ModerateBS2
The NM_002738.7(PRKCB):c.1177G>T(p.Val393Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,614,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
PRKCB
NM_002738.7 missense
NM_002738.7 missense
Scores
6
3
5
Clinical Significance
Conservation
PhyloP100: 8.19
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PP2
Missense variant where missense usually causes diseases, PRKCB
PP3
MetaRNN computational evidence supports a deleterious effect, 0.859
BS2
High AC in GnomAdExome4 at 20 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKCB | NM_002738.7 | c.1177G>T | p.Val393Leu | missense_variant | 10/17 | ENST00000643927.1 | |
PRKCB | NM_212535.3 | c.1177G>T | p.Val393Leu | missense_variant | 10/17 | ||
PRKCB | XM_047434365.1 | c.790G>T | p.Val264Leu | missense_variant | 9/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKCB | ENST00000643927.1 | c.1177G>T | p.Val393Leu | missense_variant | 10/17 | NM_002738.7 | A1 | ||
PRKCB | ENST00000321728.12 | c.1177G>T | p.Val393Leu | missense_variant | 10/17 | 1 | P4 | ||
PRKCB | ENST00000472066.1 | c.118G>T | p.Val40Leu | missense_variant | 2/5 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152208Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251288Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135816
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461866Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7AN XY: 727238
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74364
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 14, 2022 | The c.1177G>T (p.V393L) alteration is located in exon 10 (coding exon 10) of the PRKCB gene. This alteration results from a G to T substitution at nucleotide position 1177, causing the valine (V) at amino acid position 393 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;N;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
Polyphen
D;D;D;D;.
Vest4
0.72, 0.70
MutPred
Loss of methylation at K391 (P = 0.0728);Loss of methylation at K391 (P = 0.0728);Loss of methylation at K391 (P = 0.0728);Loss of methylation at K391 (P = 0.0728);.;
MVP
0.88
MPC
2.0
ClinPred
D
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at