chr11-17547448-C-T
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_001292063.2(OTOG):c.76C>T(p.Leu26=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,382,008 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: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000049 ( 0 hom. )
Consequence
OTOG
NM_001292063.2 synonymous
NM_001292063.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.170
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 -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
Variant 11-17547448-C-T is Benign according to our data. Variant chr11-17547448-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 515578.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.17 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOG | NM_001292063.2 | c.76C>T | p.Leu26= | synonymous_variant | 1/56 | ENST00000399397.6 | |
OTOG | NM_001277269.2 | c.76C>T | p.Leu26= | synonymous_variant | 1/55 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOG | ENST00000399397.6 | c.76C>T | p.Leu26= | synonymous_variant | 1/56 | 5 | NM_001292063.2 | P2 | |
OTOG | ENST00000399391.7 | c.76C>T | p.Leu26= | synonymous_variant | 1/55 | 5 | A2 |
Frequencies
GnomAD3 genomes AF: 0.000158 AC: 24AN: 152156Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000488 AC: 6AN: 1229734Hom.: 0 Cov.: 31 AF XY: 0.00000500 AC XY: 3AN XY: 599458
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GnomAD4 genome AF: 0.000158 AC: 24AN: 152274Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74470
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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 | GeneDx | Feb 22, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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BayesDel_noAF
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CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at