NM_002739.5:c.449_450delGCinsTT

Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PM1PM5PP2PP3PP5

The NM_002739.5(PRKCG):​c.449_450delGCinsTT​(p.Cys150Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C150G) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 31)

Consequence

PRKCG
NM_002739.5 missense

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.76

Publications

4 publications found
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]
PRKCG Gene-Disease associations (from GenCC):
  • spinocerebellar ataxia type 14
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 7 ACMG points.

PM1
In a zinc_finger_region Phorbol-ester/DAG-type 2 (size 50) in uniprot entity KPCG_HUMAN there are 29 pathogenic changes around while only 0 benign (100%) in NM_002739.5
PM5
Other missense variant is known to change same aminoacid residue: Variant chr19-53889936-T-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 4278058.Status of the report is criteria_provided_single_submitter, 1 stars.
PP2
Missense variant in the PRKCG gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 36 curated pathogenic missense variants (we use a threshold of 10). The gene has 5 curated benign missense variants. Gene score misZ: 3.0601 (below the threshold of 3.09). Trascript score misZ: 3.8304 (above the threshold of 3.09). GenCC associations: The gene is linked to spinocerebellar ataxia type 14.
PP3
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
PP5
Variant 19-53889937-GC-TT is Pathogenic according to our data. Variant chr19-53889937-GC-TT is described in ClinVar as [Pathogenic]. Clinvar id is 42170.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRKCGNM_002739.5 linkc.449_450delGCinsTT p.Cys150Phe missense_variant ENST00000263431.4 NP_002730.1 P05129-1
PRKCGNM_001316329.2 linkc.449_450delGCinsTT p.Cys150Phe missense_variant NP_001303258.1 P05129B7Z3W6B2R5T1A0A804HIU5
PRKCGXM_047439092.1 linkc.65_66delGCinsTT p.Cys22Phe missense_variant XP_047295048.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRKCGENST00000263431.4 linkc.449_450delGCinsTT p.Cys150Phe missense_variant 1 NM_002739.5 ENSP00000263431.3 P05129-1

Frequencies

GnomAD3 genomes
Cov.:
31
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Spinocerebellar ataxia type 14 Pathogenic:1
Apr 18, 2013
GeneReviews
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:curation

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
9.8
Mutation Taster
=0/100
disease causing

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs386134170; hg19: chr19-54393191; API