chr11-17645773-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_001292063.2(OTOG):c.8571C>T(p.Cys2857=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00001 in 1,398,538 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: not found (cov: 33)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
OTOG
NM_001292063.2 synonymous
NM_001292063.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.696
Genes affected
OTOG (HGNC:8516): (otogelin) The protein encoded by this gene is a component of the acellular membranes of the inner ear. Disruption of the orthologous mouse gene shows that it plays a role in auditory and vestibular functions. It is involved in fibrillar network organization, the anchoring of otoconial membranes and cupulae to the neuroepithelia, and likely in sound stimulation resistance. Mutations in this gene cause autosomal recessive nonsyndromic deafness, type 18B. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
?
Variant 11-17645773-C-T is Benign according to our data. Variant chr11-17645773-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 517261.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.696 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOG | NM_001292063.2 | c.8571C>T | p.Cys2857= | synonymous_variant | 56/56 | ENST00000399397.6 | |
OTOG | NM_001277269.2 | c.8607C>T | p.Cys2869= | synonymous_variant | 55/55 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOG | ENST00000399397.6 | c.8571C>T | p.Cys2857= | synonymous_variant | 56/56 | 5 | NM_001292063.2 | P2 | |
OTOG | ENST00000399391.7 | c.8607C>T | p.Cys2869= | synonymous_variant | 55/55 | 5 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.0000266 AC: 4AN: 150282Hom.: 0 AF XY: 0.0000372 AC XY: 3AN XY: 80744
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GnomAD4 exome AF: 0.0000100 AC: 14AN: 1398538Hom.: 0 Cov.: 32 AF XY: 0.0000130 AC XY: 9AN XY: 689792
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GnomAD4 genome ? Cov.: 33
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33
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 31, 2017 | p.Cys2869Cys in exon 55 of OTOG: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 2/22548 South Asi an chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadin stitute.org/). - |
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