rs16934404
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001292063.2(OTOG):c.2274C>T(p.Arg758=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0074 in 1,528,074 control chromosomes in the GnomAD database, including 347 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.022 ( 91 hom., cov: 33)
Exomes 𝑓: 0.0058 ( 256 hom. )
Consequence
OTOG
NM_001292063.2 synonymous
NM_001292063.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.15
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
?
Variant 11-17573271-C-T is Benign according to our data. Variant chr11-17573271-C-T is described in ClinVar as [Benign]. Clinvar id is 226867.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.14 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0817 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOG | NM_001292063.2 | c.2274C>T | p.Arg758= | synonymous_variant | 19/56 | ENST00000399397.6 | |
OTOG | NM_001277269.2 | c.2310C>T | p.Arg770= | synonymous_variant | 18/55 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOG | ENST00000399397.6 | c.2274C>T | p.Arg758= | synonymous_variant | 19/56 | 5 | NM_001292063.2 | P2 | |
OTOG | ENST00000399391.7 | c.2310C>T | p.Arg770= | synonymous_variant | 18/55 | 5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0217 AC: 3296AN: 152178Hom.: 91 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
3296
AN:
152178
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0176 AC: 2311AN: 130940Hom.: 73 AF XY: 0.0163 AC XY: 1162AN XY: 71224
GnomAD3 exomes
AF:
AC:
2311
AN:
130940
Hom.:
AF XY:
AC XY:
1162
AN XY:
71224
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00582 AC: 8009AN: 1375778Hom.: 256 Cov.: 32 AF XY: 0.00582 AC XY: 3940AN XY: 677446
GnomAD4 exome
AF:
AC:
8009
AN:
1375778
Hom.:
Cov.:
32
AF XY:
AC XY:
3940
AN XY:
677446
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0217 AC: 3302AN: 152296Hom.: 91 Cov.: 33 AF XY: 0.0226 AC XY: 1686AN XY: 74466
GnomAD4 genome
?
AF:
AC:
3302
AN:
152296
Hom.:
Cov.:
33
AF XY:
AC XY:
1686
AN XY:
74466
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
126
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 24, 2014 | Arg770Arg in exon 18 of OTOG: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 13.0% (26/200) of Ha n Chinese chromosomes from a broad population by the 1000 Genomes Project (http: //www.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs16934404). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 03, 2017 | 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. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 31, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
OTOG-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 07, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at