16-56192292-T-G
Variant names:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP2PP3_ModeratePP5_Moderate
The NM_020988.3(GNAO1):c.57T>G(p.Ile19Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 31)
Consequence
GNAO1
NM_020988.3 missense
NM_020988.3 missense
Scores
9
7
3
Clinical Significance
Conservation
PhyloP100: 3.72
Genes affected
GNAO1 (HGNC:4389): (G protein subunit alpha o1) The protein encoded by this gene represents the alpha subunit of the Go heterotrimeric G-protein signal-transducing complex. Defects in this gene are a cause of early-onset epileptic encephalopathy. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the GNAO1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 70 curated pathogenic missense variants (we use a threshold of 10). The gene has 43 curated benign missense variants. Gene score misZ: 3.1919 (above the threshold of 3.09). Trascript score misZ: 4.549 (above the threshold of 3.09). GenCC associations: The gene is linked to developmental and epileptic encephalopathy, 17, neurodevelopmental disorder with involuntary movements, developmental and epileptic encephalopathy, movement disorder.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.884
PP5
Variant 16-56192292-T-G is Pathogenic according to our data. Variant chr16-56192292-T-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2500270.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GNAO1 | NM_020988.3 | c.57T>G | p.Ile19Met | missense_variant | Exon 1 of 9 | ENST00000262493.12 | NP_066268.1 | |
GNAO1 | NM_138736.3 | c.57T>G | p.Ile19Met | missense_variant | Exon 1 of 8 | NP_620073.2 | ||
GNAO1 | XR_007064866.1 | n.804T>G | non_coding_transcript_exon_variant | Exon 1 of 9 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 17;C4479569:Neurodevelopmental disorder with involuntary movements Pathogenic:1
Feb 09, 2023
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Developmental and epileptic encephalopathy, 17 Pathogenic:1
Feb 09, 2023
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Pathogenic
D;.;D;.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;T;T;T;T;T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;.;H;H;.;.
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.;.;N;.;.
REVEL
Pathogenic
Sift
Uncertain
D;.;.;D;.;.
Sift4G
Pathogenic
D;.;.;D;D;.
Polyphen
D;.;D;D;.;.
Vest4
MutPred
Gain of ubiquitination at K21 (P = 0.0501);Gain of ubiquitination at K21 (P = 0.0501);Gain of ubiquitination at K21 (P = 0.0501);Gain of ubiquitination at K21 (P = 0.0501);Gain of ubiquitination at K21 (P = 0.0501);Gain of ubiquitination at K21 (P = 0.0501);
MVP
MPC
2.6
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.