rs1375924761
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_002739.5(PRKCG):βc.2004delβ(p.Asp669IlefsTer8) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,516 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ).
Frequency
Genomes: not found (cov: 30)
Exomes π: 0.0000014 ( 0 hom. )
Consequence
PRKCG
NM_002739.5 frameshift
NM_002739.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.957
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 4 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0435 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKCG | NM_002739.5 | c.2004del | p.Asp669IlefsTer8 | frameshift_variant | 18/18 | ENST00000263431.4 | |
PRKCG | NM_001316329.2 | c.2004del | p.Asp669IlefsTer8 | frameshift_variant | 18/19 | ||
PRKCG | XM_047439092.1 | c.1620del | p.Asp541IlefsTer8 | frameshift_variant | 19/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKCG | ENST00000263431.4 | c.2004del | p.Asp669IlefsTer8 | frameshift_variant | 18/18 | 1 | NM_002739.5 | P1 | |
PRKCG | ENST00000682028.1 | c.2004del | p.Asp669IlefsTer8 | frameshift_variant | 18/19 | ||||
PRKCG | ENST00000683513.1 | c.1896del | p.Asp633IlefsTer8 | frameshift_variant | 17/17 | ||||
PRKCG | ENST00000682676.1 | n.1405del | non_coding_transcript_exon_variant | 10/10 |
Frequencies
GnomAD3 genomes ? Cov.: 30
GnomAD3 genomes
?
Cov.:
30
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461516Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727066
GnomAD4 exome
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1461516
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32
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1
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727066
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GnomAD4 genome ? Cov.: 30
GnomAD4 genome
?
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30
Bravo
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 23, 2016 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 03, 2023 | Not observed at significant frequency in large population cohorts (gnomAD); Frameshift variant predicted to result in protein truncation in a gene for which loss-of-function is not a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
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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