rs764159927
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_001292063.2(OTOG):c.4641G>T(p.Glu1547Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000806 in 1,538,114 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001292063.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOG | NM_001292063.2 | c.4641G>T | p.Glu1547Asp | missense_variant | 36/56 | ENST00000399397.6 | |
OTOG | NM_001277269.2 | c.4677G>T | p.Glu1559Asp | missense_variant | 35/55 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOG | ENST00000399397.6 | c.4641G>T | p.Glu1547Asp | missense_variant | 36/56 | 5 | NM_001292063.2 | P2 | |
OTOG | ENST00000399391.7 | c.4677G>T | p.Glu1559Asp | missense_variant | 35/55 | 5 | A2 | ||
OTOG | ENST00000342528.2 | n.1979G>T | non_coding_transcript_exon_variant | 12/22 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000586 AC: 89AN: 152006Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000336 AC: 47AN: 139704Hom.: 1 AF XY: 0.000268 AC XY: 20AN XY: 74670
GnomAD4 exome AF: 0.000830 AC: 1151AN: 1386108Hom.: 1 Cov.: 31 AF XY: 0.000795 AC XY: 542AN XY: 681988
GnomAD4 genome ? AF: 0.000586 AC: 89AN: 152006Hom.: 1 Cov.: 32 AF XY: 0.000566 AC XY: 42AN XY: 74230
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:3
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 02, 2020 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | OTOG: BP4, BS2 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jan 05, 2023 | Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity (http://gnomad.broadinstitute.org). Computational tools predict that this variant is not damaging. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 21, 2023 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 03, 2017 | The p.Glu1559Asp variant in OTOG has not been previously reported in individuals with hearing loss, but has been identified in 49/62630 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs764159927). Although this variant has been seen in the general population, it s frequency is not high enough to rule out a pathogenic role. Computational pred iction tools and conservation analysis suggest that the p.Glu1559Asp variant may not impact the protein, though this information is not predictive enough to rul e out pathogenicity. In summary, the clinical significance of the p.Glu1559Asp v ariant is uncertain. ACMG/AMP Criteria applied: BP4 (Richards 2015). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at