rs117005078
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP3BP6
The NM_001292063.2(OTOG):c.3683C>T(p.Pro1228Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00483 in 1,550,638 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P1228P) has been classified as Likely benign.
Frequency
Consequence
NM_001292063.2 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOG | NM_001292063.2 | c.3683C>T | p.Pro1228Leu | missense_variant, splice_region_variant | 31/56 | ENST00000399397.6 | |
OTOG | NM_001277269.2 | c.3719C>T | p.Pro1240Leu | missense_variant, splice_region_variant | 30/55 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOG | ENST00000399397.6 | c.3683C>T | p.Pro1228Leu | missense_variant, splice_region_variant | 31/56 | 5 | NM_001292063.2 | P2 | |
OTOG | ENST00000399391.7 | c.3719C>T | p.Pro1240Leu | missense_variant, splice_region_variant | 30/55 | 5 | A2 | ||
OTOG | ENST00000342528.2 | n.1048-2539C>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00330 AC: 502AN: 152206Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00273 AC: 409AN: 149550Hom.: 0 AF XY: 0.00241 AC XY: 194AN XY: 80466
GnomAD4 exome AF: 0.00500 AC: 6985AN: 1398314Hom.: 17 Cov.: 31 AF XY: 0.00487 AC XY: 3361AN XY: 689684
GnomAD4 genome ? AF: 0.00330 AC: 502AN: 152324Hom.: 0 Cov.: 33 AF XY: 0.00305 AC XY: 227AN XY: 74488
ClinVar
Submissions by phenotype
not provided Benign:4
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | OTOG: BS1 - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 12, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 18, 2019 | This variant is associated with the following publications: (PMID: 30097855) - |
Meniere disease Uncertain:1
Uncertain significance, criteria provided, single submitter | case-control | Otology & Neurotology- Genomics of vestibular disorders (CTS-495), Jose Antonio López Escámez, Centro Pfizer - Universidad de Granada - Junta de Andalucía de Genómica e Investigación Oncológica (GENYO) | Jan 01, 2020 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 13, 2017 | p.Pro1240Leu in exon 30 of OTOG: This variant is not expected to have clinical significance because it has been identified in 0.6% (384/67268) of European chro mosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute .org; dbSNP rs117005078). Furthermore, this variant has been reported by our la boratory in 10 individuals with hearing loss, including 4 with an alternate gene tic etiology identified. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at