rs461179
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_144672.4(OTOA):c.2229C>T(p.Ala743=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 141,714 control chromosomes in the GnomAD database, including 1,123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.11 ( 1123 hom., cov: 30)
Exomes 𝑓: 0.030 ( 5452 hom. )
Failed GnomAD Quality Control
Consequence
OTOA
NM_144672.4 synonymous
NM_144672.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.31
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]
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=-0.65).
BP6
Variant 16-21730858-C-T is Benign according to our data. Variant chr16-21730858-C-T is described in ClinVar as [Benign]. Clinvar id is 164827.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-21730858-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-3.31 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOA | NM_144672.4 | c.2229C>T | p.Ala743= | synonymous_variant | 21/29 | ENST00000646100.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOA | ENST00000646100.2 | c.2229C>T | p.Ala743= | synonymous_variant | 21/29 | NM_144672.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.106 AC: 14999AN: 141612Hom.: 1116 Cov.: 30
GnomAD3 genomes
AF:
AC:
14999
AN:
141612
Hom.:
Cov.:
30
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: 0.0305 AC: 7072AN: 232152Hom.: 1293 AF XY: 0.0293 AC XY: 3689AN XY: 125858
GnomAD3 exomes
AF:
AC:
7072
AN:
232152
Hom.:
AF XY:
AC XY:
3689
AN XY:
125858
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 Data not reliable, filtered out with message: AS_VQSR AF: 0.0295 AC: 39417AN: 1334280Hom.: 5452 Cov.: 29 AF XY: 0.0322 AC XY: 21326AN XY: 661458
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
39417
AN:
1334280
Hom.:
Cov.:
29
AF XY:
AC XY:
21326
AN XY:
661458
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: 0.106 AC: 15010AN: 141714Hom.: 1123 Cov.: 30 AF XY: 0.110 AC XY: 7556AN XY: 68698
GnomAD4 genome
AF:
AC:
15010
AN:
141714
Hom.:
Cov.:
30
AF XY:
AC XY:
7556
AN XY:
68698
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.:
ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 02, 2015 | p.Ala743Ala in Exon 20 of OTOA: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence and it has been identified in 0.4% (490/11461 0) of chromosomes including 62 individuals who were homozygous by the Exome Aggr egation Consortium (ExAC, http://exac.broadinstitute.org; rs139312489). - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 10, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 26, 2018 | 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 | PreventionGenetics, part of Exact Sciences | Feb 29, 2016 | - - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Autosomal recessive nonsyndromic hearing loss 22 Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 07, 2023 | - - |
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