16-56192252-G-T
Variant names:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP2PP3_ModeratePP5
The NM_020988.3(GNAO1):c.17G>T(p.Ser6Ile) 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. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
GNAO1
NM_020988.3 missense
NM_020988.3 missense
Scores
15
3
1
Clinical Significance
Conservation
PhyloP100: 9.53
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 6 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, 0.934
PP5
Variant 16-56192252-G-T is Pathogenic according to our data. Variant chr16-56192252-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 1802165.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GNAO1 | NM_020988.3 | c.17G>T | p.Ser6Ile | missense_variant | Exon 1 of 9 | ENST00000262493.12 | NP_066268.1 | |
GNAO1 | NM_138736.3 | c.17G>T | p.Ser6Ile | missense_variant | Exon 1 of 8 | NP_620073.2 | ||
GNAO1 | XR_007064866.1 | n.764G>T | non_coding_transcript_exon_variant | Exon 1 of 9 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 1444788Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 718652
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
AC:
0
AN:
1444788
Hom.:
Cov.:
29
AF XY:
AC XY:
0
AN XY:
718652
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
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Gnomad4 ASJ exome
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Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 OTH exome
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GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 17 Pathogenic:1
-
Key Laboratory of Neurobehavioral Science for Children, Children's Hospital Affiliated of Zhengzhou University
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: research
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;.;D;.;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
.;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;.;H;H;.;.
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;.;.;D;.;.
REVEL
Pathogenic
Sift
Pathogenic
D;.;.;D;.;.
Sift4G
Pathogenic
D;.;.;D;D;.
Polyphen
D;.;D;D;.;.
Vest4
MutPred
Loss of disorder (P = 0.0213);Loss of disorder (P = 0.0213);Loss of disorder (P = 0.0213);Loss of disorder (P = 0.0213);Loss of disorder (P = 0.0213);Loss of disorder (P = 0.0213);
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
DS_AG_spliceai
Position offset: 6
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.