19-53882541-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4

The NM_002739.5(PRKCG):​c.47G>A​(p.Arg16Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

PRKCG
NM_002739.5 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.37
Variant links:
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]

Genome browser will be placed here

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=0.27005348).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRKCGNM_002739.5 linkuse as main transcriptc.47G>A p.Arg16Gln missense_variant 1/18 ENST00000263431.4
PRKCGNM_001316329.2 linkuse as main transcriptc.47G>A p.Arg16Gln missense_variant 1/19
PRKCGXM_047439092.1 linkuse as main transcriptc.-322-16G>A splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRKCGENST00000263431.4 linkuse as main transcriptc.47G>A p.Arg16Gln missense_variant 1/181 NM_002739.5 P1P05129-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
250960
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135834
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461866
Hom.:
0
Cov.:
29
AF XY:
0.00000688
AC XY:
5
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000151

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 19, 2023The c.47G>A (p.R16Q) alteration is located in exon 1 (coding exon 1) of the PRKCG gene. This alteration results from a G to A substitution at nucleotide position 47, causing the arginine (R) at amino acid position 16 to be replaced by a glutamine (Q). 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
Benign
0.15
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.32
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.27
T
Eigen
Benign
-0.20
Eigen_PC
Benign
-0.062
FATHMM_MKL
Benign
0.29
N
LIST_S2
Benign
0.62
T
M_CAP
Uncertain
0.27
D
MetaRNN
Benign
0.27
T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
1.0
L
MutationTaster
Benign
0.51
D;D;D
PrimateAI
Pathogenic
0.80
D
PROVEAN
Benign
-0.61
N
REVEL
Benign
0.14
Sift
Benign
0.13
T
Sift4G
Benign
0.37
T
Polyphen
0.70
P
Vest4
0.23
MutPred
0.41
Loss of helix (P = 0.0304);
MVP
0.71
MPC
1.7
ClinPred
0.39
T
GERP RS
4.1
Varity_R
0.10
gMVP
0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1360731511; hg19: chr19-54385795; API