rs1177582167
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_002739.5(PRKCG):c.1858G>A(p.Glu620Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000014 in 1,571,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 29)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
PRKCG
NM_002739.5 missense
NM_002739.5 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 7.89
Genes affected
PRKCG (HGNC:9402): (protein kinase C gamma) 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 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 distinct roles in cells. The protein encoded by this gene is one of the PKC family members. This protein kinase is expressed solely in the brain and spinal cord and its localization is restricted to neurons. It has been demonstrated that several neuronal functions, including long term potentiation (LTP) and long term depression (LTD), specifically require this kinase. Knockout studies in mice also suggest that this kinase may be involved in neuropathic pain development. Defects in this protein have been associated with neurodegenerative disorder spinocerebellar ataxia-14 (SCA14). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), PRKCG. . Gene score misZ 3.0601 (greater than the threshold 3.09). Trascript score misZ 3.8304 (greater than threshold 3.09). GenCC has associacion of gene with spinocerebellar ataxia type 14.
BP4
Computational evidence support a benign effect (MetaRNN=0.30517462).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRKCG | NM_002739.5 | c.1858G>A | p.Glu620Lys | missense_variant | 17/18 | ENST00000263431.4 | NP_002730.1 | |
PRKCG | NM_001316329.2 | c.1858G>A | p.Glu620Lys | missense_variant | 17/19 | NP_001303258.1 | ||
PRKCG | XM_047439092.1 | c.1474G>A | p.Glu492Lys | missense_variant | 18/20 | XP_047295048.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRKCG | ENST00000263431.4 | c.1858G>A | p.Glu620Lys | missense_variant | 17/18 | 1 | NM_002739.5 | ENSP00000263431.3 | ||
PRKCG | ENST00000682028.1 | c.1858G>A | p.Glu620Lys | missense_variant | 17/19 | ENSP00000507230.1 | ||||
PRKCG | ENST00000683513.1 | c.1750G>A | p.Glu584Lys | missense_variant | 16/17 | ENSP00000506809.1 | ||||
PRKCG | ENST00000682676.1 | n.1259G>A | non_coding_transcript_exon_variant | 9/10 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 151958Hom.: 0 Cov.: 29
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GnomAD3 exomes AF: 0.0000161 AC: 3AN: 185974Hom.: 0 AF XY: 0.0000201 AC XY: 2AN XY: 99526
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GnomAD4 exome AF: 0.0000134 AC: 19AN: 1419640Hom.: 0 Cov.: 31 AF XY: 0.0000171 AC XY: 12AN XY: 702310
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 151958Hom.: 0 Cov.: 29 AF XY: 0.0000135 AC XY: 1AN XY: 74214
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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 | Genetic Services Laboratory, University of Chicago | Nov 10, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of MoRF binding (P = 0.0038);
MVP
MPC
ClinPred
T
GERP RS
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