rs463192
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_144672.4(OTOA):c.2431+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000163 in 1,614,030 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00094 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000082 ( 1 hom. )
Consequence
OTOA
NM_144672.4 intron
NM_144672.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.411
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 -10 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 16-21736401-T-C is Benign according to our data. Variant chr16-21736401-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 226856.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-21736401-T-C is described in Lovd as [Likely_benign].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOA | NM_144672.4 | c.2431+11T>C | intron_variant | ENST00000646100.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOA | ENST00000646100.2 | c.2431+11T>C | intron_variant | NM_144672.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000946 AC: 144AN: 152150Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000179 AC: 45AN: 251426Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135892
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GnomAD4 exome AF: 0.0000821 AC: 120AN: 1461762Hom.: 1 Cov.: 32 AF XY: 0.0000825 AC XY: 60AN XY: 727182
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GnomAD4 genome ? AF: 0.000939 AC: 143AN: 152268Hom.: 0 Cov.: 32 AF XY: 0.000806 AC XY: 60AN XY: 74476
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 08, 2015 | c.2431+11T>C in intron 21 of OTOA: This variant is not expected to have clinical significance because it is not located within the splice consensus sequence. It has been identified in 0.2% (21/10400) of African chromosomes by the Exome Aggr egation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs463192). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 19, 2020 | - - |
Computational scores
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Name
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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