16-56192319-C-T
Variant names:
Variant summary
Our verdict is Benign. The variant received -7 ACMG points: 2P and 9B. PM2BP4_ModerateBP6_ModerateBP7BS2
The NM_020988.3(GNAO1):c.84C>T(p.Ile28Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,457,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
GNAO1
NM_020988.3 synonymous
NM_020988.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.11
Publications
0 publications found
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 was made for transcript
Our verdict: Benign. The variant received -7 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
Variant 16-56192319-C-T is Benign according to our data. Variant chr16-56192319-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2966319.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.12 with no splicing effect.
BS2
High AC in GnomAdExome4 at 5 AD gene.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| GNAO1 | NM_020988.3 | c.84C>T | p.Ile28Ile | synonymous_variant | Exon 1 of 9 | ENST00000262493.12 | NP_066268.1 | |
| GNAO1 | NM_138736.3 | c.84C>T | p.Ile28Ile | synonymous_variant | Exon 1 of 8 | NP_620073.2 | ||
| GNAO1 | XR_007064866.1 | n.831C>T | non_coding_transcript_exon_variant | Exon 1 of 9 | ||||
| GNAO1 | XM_011523003.4 | c.-635C>T | upstream_gene_variant | XP_011521305.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 152090Hom.: 0 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152090
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000343 AC: 5AN: 1457264Hom.: 0 Cov.: 29 AF XY: 0.00000552 AC XY: 4AN XY: 725194 show subpopulations
GnomAD4 exome
AF:
AC:
5
AN:
1457264
Hom.:
Cov.:
29
AF XY:
AC XY:
4
AN XY:
725194
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33412
American (AMR)
AF:
AC:
0
AN:
44708
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26108
East Asian (EAS)
AF:
AC:
0
AN:
39682
South Asian (SAS)
AF:
AC:
0
AN:
86156
European-Finnish (FIN)
AF:
AC:
0
AN:
52508
Middle Eastern (MID)
AF:
AC:
0
AN:
5756
European-Non Finnish (NFE)
AF:
AC:
5
AN:
1108704
Other (OTH)
AF:
AC:
0
AN:
60230
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.495
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1AN XY: 74416 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
152204
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
74416
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
41526
American (AMR)
AF:
AC:
0
AN:
15300
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5154
South Asian (SAS)
AF:
AC:
0
AN:
4824
European-Finnish (FIN)
AF:
AC:
0
AN:
10608
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68008
Other (OTH)
AF:
AC:
1
AN:
2106
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy Benign:1
Feb 05, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
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
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