rs72640475
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_144672.4(OTOA):c.2238G>A(p.Thr746=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 146,692 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 Benign (★★).
Frequency
Genomes: 𝑓 0.015 ( 0 hom., cov: 31)
Exomes 𝑓: 0.017 ( 421 hom. )
Failed GnomAD Quality Control
Consequence
OTOA
NM_144672.4 synonymous
NM_144672.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.08
Genes affected
OTOA (HGNC:16378): (otoancorin) The protein encoded by this gene is specifically expressed in the inner ear, and is located at the interface between the apical surface of the inner ear sensory epithelia and their overlying acellular gels. It is prposed that this protein is involved in the attachment of the inner ear acellular gels to the apical surface of the underlying nonsensory cells. Mutations in this gene are associated with autosomal recessive deafness type 22 (DFNB22). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
?
Variant 16-21730867-G-A is Benign according to our data. Variant chr16-21730867-G-A is described in ClinVar as [Benign]. Clinvar id is 47953.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOA | NM_144672.4 | c.2238G>A | p.Thr746= | synonymous_variant | 21/29 | ENST00000646100.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOA | ENST00000646100.2 | c.2238G>A | p.Thr746= | synonymous_variant | 21/29 | NM_144672.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0145 AC: 2126AN: 146584Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0533 AC: 12804AN: 240440Hom.: 346 AF XY: 0.0454 AC XY: 5897AN XY: 129832
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0165 AC: 23282AN: 1410698Hom.: 421 Cov.: 29 AF XY: 0.0159 AC XY: 11157AN XY: 702380
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GnomAD4 genome ? AF: 0.0146 AC: 2136AN: 146692Hom.: 0 Cov.: 31 AF XY: 0.0175 AC XY: 1249AN XY: 71226
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 13, 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. - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | Thr746Thr in Exon 20 of OTOA: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 0.3% (22/6966) of Euro pean American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs76494517). - |
Autosomal recessive nonsyndromic hearing loss 22 Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Aug 29, 2018 | - - |
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
DS_AL_spliceai
Position offset: -30
Find out detailed SpliceAI scores and Pangolin per-transcript scores at