16-56351496-T-A
Position:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP2PP3_StrongPP5
The NM_020988.3(GNAO1):c.836T>A(p.Ile279Asn) 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. 11/18 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Consequence
GNAO1
NM_020988.3 missense
NM_020988.3 missense
Scores
15
1
1
Clinical Significance
Conservation
PhyloP100: 8.02
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 Pathogenic. Variant got 10 ACMG points.
PM1
In a hotspot region, there are 4 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 6 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, 0.982
PP5
Variant 16-56351496-T-A is Pathogenic according to our data. Variant chr16-56351496-T-A is described in ClinVar as [Pathogenic]. Clinvar id is 66112.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-56351496-T-A is described in Lovd as [Pathogenic]. Variant chr16-56351496-T-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNAO1 | NM_020988.3 | c.836T>A | p.Ile279Asn | missense_variant | 7/9 | ENST00000262493.12 | |
GNAO1 | XM_011523003.4 | c.710T>A | p.Ile237Asn | missense_variant | 7/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNAO1 | ENST00000262493.12 | c.836T>A | p.Ile279Asn | missense_variant | 7/9 | 1 | NM_020988.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 17 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 05, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;D;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;H;.;.;.
MutationTaster
Benign
D
PROVEAN
Pathogenic
D;.;.;.;.
REVEL
Pathogenic
Sift
Pathogenic
D;.;.;.;.
Sift4G
Pathogenic
D;.;.;.;.
Polyphen
D;D;.;.;.
Vest4
MutPred
Gain of disorder (P = 0.0152);Gain of disorder (P = 0.0152);.;.;.;
MVP
ClinPred
D
GERP RS
Varity_R
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