rs575344158
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7
The NM_001292063.2(OTOG):c.1050C>T(p.His350=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000514 in 1,550,464 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00051 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00051 ( 1 hom. )
Consequence
OTOG
NM_001292063.2 synonymous
NM_001292063.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.370
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 -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
Variant 11-17558591-C-T is Benign according to our data. Variant chr11-17558591-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 514533.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.37 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OTOG | NM_001292063.2 | c.1050C>T | p.His350= | synonymous_variant | 10/56 | ENST00000399397.6 | NP_001278992.1 | |
OTOG | NM_001277269.2 | c.1086C>T | p.His362= | synonymous_variant | 9/55 | NP_001264198.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OTOG | ENST00000399397.6 | c.1050C>T | p.His350= | synonymous_variant | 10/56 | 5 | NM_001292063.2 | ENSP00000382329 | P2 | |
OTOG | ENST00000399391.7 | c.1086C>T | p.His362= | synonymous_variant | 9/55 | 5 | ENSP00000382323 | A2 | ||
OTOG | ENST00000485669.1 | n.534C>T | non_coding_transcript_exon_variant | 3/3 | 4 | |||||
OTOG | ENST00000498332.5 | n.956C>T | non_coding_transcript_exon_variant | 9/16 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000519 AC: 79AN: 152232Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.000850 AC: 125AN: 147066Hom.: 0 AF XY: 0.000958 AC XY: 76AN XY: 79340
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GnomAD4 exome AF: 0.000514 AC: 719AN: 1398114Hom.: 1 Cov.: 33 AF XY: 0.000500 AC XY: 345AN XY: 689588
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GnomAD4 genome AF: 0.000512 AC: 78AN: 152350Hom.: 1 Cov.: 33 AF XY: 0.000550 AC XY: 41AN XY: 74496
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 02, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2022 | OTOG: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 05, 2020 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 10, 2017 | p.His362His 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. It has also been identified in 0.4% (35/8398) of Ashkenazi Jewish chromosomes by the Genome Aggregation Database (gnomAD, htt p://gnomad.broadinstitute.org; dbSNP rs575344158). - |
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