rs1555507383
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PP2PP3_StrongPP5_Moderate
The NM_020988.3(GNAO1):c.550G>C(p.Gly184Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 34)
Consequence
GNAO1
NM_020988.3 missense
NM_020988.3 missense
Scores
17
1
Clinical Significance
Conservation
PhyloP100: 9.94
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PM1
?
In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 3 uncertain in NM_020988.3
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, GNAO1
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.988
PP5
?
Variant 16-56334814-G-C is Pathogenic according to our data. Variant chr16-56334814-G-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 521928.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNAO1 | NM_020988.3 | c.550G>C | p.Gly184Arg | missense_variant | 5/9 | ENST00000262493.12 | |
GNAO1 | NM_138736.3 | c.550G>C | p.Gly184Arg | missense_variant | 5/8 | ||
GNAO1 | XM_011523003.4 | c.424G>C | p.Gly142Arg | missense_variant | 5/9 | ||
GNAO1 | XR_007064866.1 | n.1297G>C | non_coding_transcript_exon_variant | 5/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNAO1 | ENST00000262493.12 | c.550G>C | p.Gly184Arg | missense_variant | 5/9 | 1 | NM_020988.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome ? Cov.: 34
GnomAD4 genome
?
Cov.:
34
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 24, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Pathogenic
D;D;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;H;H;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;.;D;.
REVEL
Pathogenic
Sift
Pathogenic
D;.;D;.
Sift4G
Pathogenic
D;.;D;.
Polyphen
D;D;D;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0135);Gain of MoRF binding (P = 0.0135);Gain of MoRF binding (P = 0.0135);.;
MVP
MPC
2.9
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