rs876657550
Positions:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_001292063.2(OTOG):c.1024C>T(p.Leu342=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000358 in 1,398,184 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: 0.0000036 ( 0 hom. )
Consequence
OTOG
NM_001292063.2 synonymous
NM_001292063.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.863
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 Benign. Variant got -9 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 11-17558565-C-T is Benign according to our data. Variant chr11-17558565-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 227760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.863 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOG | NM_001292063.2 | c.1024C>T | p.Leu342= | synonymous_variant | 10/56 | ENST00000399397.6 | |
OTOG | NM_001277269.2 | c.1060C>T | p.Leu354= | synonymous_variant | 9/55 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOG | ENST00000399397.6 | c.1024C>T | p.Leu342= | synonymous_variant | 10/56 | 5 | NM_001292063.2 | P2 | |
OTOG | ENST00000399391.7 | c.1060C>T | p.Leu354= | synonymous_variant | 9/55 | 5 | A2 | ||
OTOG | ENST00000485669.1 | n.508C>T | non_coding_transcript_exon_variant | 3/3 | 4 | ||||
OTOG | ENST00000498332.5 | n.930C>T | non_coding_transcript_exon_variant | 9/16 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 0.00000358 AC: 5AN: 1398184Hom.: 0 Cov.: 33 AF XY: 0.00000580 AC XY: 4AN XY: 689626
GnomAD4 exome
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5
AN:
1398184
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33
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AC XY:
4
AN XY:
689626
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
Bravo
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
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 | Feb 25, 2016 | p.Leu354Leu in exon 9 of OTOG: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 08, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
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