rs142102704
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_020988.3(GNAO1):c.1017C>A(p.Val339=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000645 in 1,613,640 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00035 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000034 ( 1 hom. )
Consequence
GNAO1
NM_020988.3 synonymous
NM_020988.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.82
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 Benign. Variant got -18 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
?
Variant 16-56355005-C-A is Benign according to our data. Variant chr16-56355005-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 530558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000355 (54/152194) while in subpopulation AFR AF= 0.00125 (52/41502). AF 95% confidence interval is 0.000981. There are 0 homozygotes in gnomad4. There are 27 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 54 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNAO1 | NM_020988.3 | c.1017C>A | p.Val339= | synonymous_variant | 8/9 | ENST00000262493.12 | |
GNAO1 | XM_011523003.4 | c.891C>A | p.Val297= | synonymous_variant | 8/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNAO1 | ENST00000262493.12 | c.1017C>A | p.Val339= | synonymous_variant | 8/9 | 1 | NM_020988.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000355 AC: 54AN: 152076Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000875 AC: 22AN: 251430Hom.: 1 AF XY: 0.0000662 AC XY: 9AN XY: 135892
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GnomAD4 exome AF: 0.0000342 AC: 50AN: 1461446Hom.: 1 Cov.: 30 AF XY: 0.0000248 AC XY: 18AN XY: 727040
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GnomAD4 genome ? AF: 0.000355 AC: 54AN: 152194Hom.: 0 Cov.: 31 AF XY: 0.000363 AC XY: 27AN XY: 74392
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 31, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Early infantile epileptic encephalopathy with suppression bursts Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2023 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 19, 2020 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at