16-24154793-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3
The NM_002738.7(PRKCB):c.1175G>A(p.Arg392Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,086 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
PRKCB
NM_002738.7 missense
NM_002738.7 missense
Scores
9
5
Clinical Significance
Conservation
PhyloP100: 10.0
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 Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, PRKCB
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.754
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKCB | NM_002738.7 | c.1175G>A | p.Arg392Gln | missense_variant | 10/17 | ENST00000643927.1 | |
PRKCB | NM_212535.3 | c.1175G>A | p.Arg392Gln | missense_variant | 10/17 | ||
PRKCB | XM_047434365.1 | c.788G>A | p.Arg263Gln | missense_variant | 9/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKCB | ENST00000643927.1 | c.1175G>A | p.Arg392Gln | missense_variant | 10/17 | NM_002738.7 | A1 | ||
PRKCB | ENST00000321728.12 | c.1175G>A | p.Arg392Gln | missense_variant | 10/17 | 1 | P4 | ||
PRKCB | ENST00000472066.1 | c.116G>A | p.Arg39Gln | missense_variant | 2/5 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152224Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251266Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135798
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461862Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727234
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74368
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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 | Aug 02, 2023 | The c.1175G>A (p.R392Q) alteration is located in exon 10 (coding exon 10) of the PRKCB gene. This alteration results from a G to A substitution at nucleotide position 1175, causing the arginine (R) at amino acid position 392 to be replaced by a glutamine (Q). 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
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
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
0.89, 0.79
MutPred
Gain of catalytic residue at R392 (P = 0.0072);Gain of catalytic residue at R392 (P = 0.0072);Gain of catalytic residue at R392 (P = 0.0072);Gain of catalytic residue at R392 (P = 0.0072);.;
MVP
0.91
MPC
2.4
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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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