rs7936354
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001292063.2(OTOG):c.3350C>T(p.Pro1117Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00757 in 1,550,440 control chromosomes in the GnomAD database, including 736 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.039 ( 418 hom., cov: 32)
Exomes 𝑓: 0.0042 ( 318 hom. )
Consequence
OTOG
NM_001292063.2 missense
NM_001292063.2 missense
Scores
1
11
6
Clinical Significance
Conservation
PhyloP100: 5.63
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.002730459).
BP6
Variant 11-17594108-C-T is Benign according to our data. Variant chr11-17594108-C-T is described in ClinVar as [Benign]. Clinvar id is 226884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OTOG | NM_001292063.2 | c.3350C>T | p.Pro1117Leu | missense_variant | 28/56 | ENST00000399397.6 | NP_001278992.1 | |
OTOG | NM_001277269.2 | c.3386C>T | p.Pro1129Leu | missense_variant | 27/55 | NP_001264198.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OTOG | ENST00000399397.6 | c.3350C>T | p.Pro1117Leu | missense_variant | 28/56 | 5 | NM_001292063.2 | ENSP00000382329 | P2 | |
OTOG | ENST00000399391.7 | c.3386C>T | p.Pro1129Leu | missense_variant | 27/55 | 5 | ENSP00000382323 | A2 | ||
OTOG | ENST00000342528.2 | n.715C>T | non_coding_transcript_exon_variant | 5/22 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0389 AC: 5921AN: 152080Hom.: 418 Cov.: 32
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GnomAD3 exomes AF: 0.00824 AC: 1230AN: 149206Hom.: 74 AF XY: 0.00658 AC XY: 529AN XY: 80368
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GnomAD4 exome AF: 0.00416 AC: 5816AN: 1398242Hom.: 318 Cov.: 32 AF XY: 0.00368 AC XY: 2539AN XY: 689648
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GnomAD4 genome AF: 0.0389 AC: 5927AN: 152198Hom.: 418 Cov.: 32 AF XY: 0.0375 AC XY: 2788AN XY: 74440
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 30, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 23, 2018 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 24, 2014 | Pro1129Leu in exon 27 of OTOG: This variant is not expected to have clinical sig nificance because it has been identified in 15.5% (30/194) of Luhya (Kenyan) chr omosomes from a broad population by the 1000 Genomes Project (http://www.ncbi.nl m.nih.gov/projects/SNP; dbSNP rs7936354). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 05, 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. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.
REVEL
Uncertain
Sift
Uncertain
D;.
Sift4G
Uncertain
D;D
Vest4
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
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