rs461179

Variant names:

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.Ala743Ala) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -3.31

Variant links:

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]

OTOA links:

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 rank	MANE	Protein	UniProt
OTOA	NM_144672.4 link	c.2229C>T	p.Ala743Ala	synonymous_variant	Exon 21 of 29	ENST00000646100.2	NP_653273.3	Q05BM7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTOA	ENST00000646100.2 link	c.2229C>T	p.Ala743Ala	synonymous_variant	Exon 21 of 29		NM_144672.4	ENSP00000496564.2		Q7RTW8-5

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

14999

AN:

141612

Hom.:

1116

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0348

Gnomad AMI

AF:

0.0738

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.172

Gnomad EAS

AF:

0.232

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.158

Gnomad MID

AF:

0.157

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.110

GnomAD3 exomes

AF:

0.0305

AC:

7072

AN:

232152

Hom.:

1293

AF XY:

0.0293

AC XY:

3689

AN XY:

125858

show subpopulations

Gnomad AFR exome

AF:

0.00931

Gnomad AMR exome

AF:

0.0340

Gnomad ASJ exome

AF:

0.0228

Gnomad EAS exome

AF:

0.0932

Gnomad SAS exome

AF:

0.0477

Gnomad FIN exome

AF:

0.0206

Gnomad NFE exome

AF:

0.0210

Gnomad OTH exome

AF:

0.0386

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0295

AC:

39417

AN:

1334280

Hom.:

5452

Cov.:

AF XY:

0.0322

AC XY:

21326

AN XY:

661458

show subpopulations

Gnomad4 AFR exome

AF:

0.0100

Gnomad4 AMR exome

AF:

0.0414

Gnomad4 ASJ exome

AF:

0.0636

Gnomad4 EAS exome

AF:

0.111

Gnomad4 SAS exome

AF:

0.0881

Gnomad4 FIN exome

AF:

0.0702

Gnomad4 NFE exome

AF:

0.0200

Gnomad4 OTH exome

AF:

0.0415

GnomAD4 genome

AF:

0.106

AC:

15010

AN:

141714

Hom.:

1123

Cov.:

AF XY:

0.110

AC XY:

7556

AN XY:

68698

show subpopulations

Gnomad4 AFR

AF:

0.0351

Gnomad4 AMR

AF:

0.128

Gnomad4 ASJ

AF:

0.172

Gnomad4 EAS

AF:

0.231

Gnomad4 SAS

AF:

0.220

Gnomad4 FIN

AF:

0.158

Gnomad4 NFE

AF:

0.120

Gnomad4 OTH

AF:

0.110

Alfa

AF:

0.115

Hom.:

278

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Mar 02, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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). -

Feb 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Feb 29, 2016

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 10, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Autosomal recessive nonsyndromic hearing loss 22

Benign:1

Nov 07, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.070

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over