chr16-21687628-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_144672.4(OTOA):c.615C>T(p.Arg205Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0352 in 1,611,076 control chromosomes in the GnomAD database, including 1,206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 105 hom., cov: 31)

Exomes 𝑓: 0.035 ( 1101 hom. )

Consequence

OTOA
NM_144672.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.63

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 22
Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Laboratory for Molecular Medicine, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
nonsyndromic genetic hearing loss
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

OTOA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 16-21687628-C-T is Benign according to our data. Variant chr16-21687628-C-T is described in ClinVar as Benign. ClinVar VariationId is 47955.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.63 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOA	NM_144672.4 link	c.615C>T	p.Arg205Arg	synonymous_variant	Exon 8 of 29	ENST00000646100.2	NP_653273.3
OTOA	NM_001161683.2 link	c.378C>T	p.Arg126Arg	synonymous_variant	Exon 3 of 24		NP_001155155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTOA	ENST00000646100.2 link	c.615C>T	p.Arg205Arg	synonymous_variant	Exon 8 of 29		NM_144672.4	ENSP00000496564.2

Frequencies

GnomAD3 genomes

AF:

0.0339

AC:

5100

AN:

150456

Hom.:

105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0284

Gnomad AMI

AF:

0.0187

Gnomad AMR

AF:

0.0409

Gnomad ASJ

AF:

0.0257

Gnomad EAS

AF:

0.00157

Gnomad SAS

AF:

0.0101

Gnomad FIN

AF:

0.0367

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0393

Gnomad OTH

AF:

0.0439

GnomAD2 exomes

AF:

0.0305

AC:

7640

AN:

250478

AF XY:

0.0310

show subpopulations

Gnomad AFR exome

AF:

0.0266

Gnomad AMR exome

AF:

0.0273

Gnomad ASJ exome

AF:

0.0312

Gnomad EAS exome

AF:

0.00142

Gnomad FIN exome

AF:

0.0349

Gnomad NFE exome

AF:

0.0408

Gnomad OTH exome

AF:

0.0388

GnomAD4 exome

AF:

0.0354

AC:

51649

AN:

1460578

Hom.:

1101

Cov.:

AF XY:

0.0349

AC XY:

25375

AN XY:

726592

show subpopulations

African (AFR)

AF:

0.0299

AC:

1001

AN:

33452

American (AMR)

AF:

0.0279

AC:

1245

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.0305

AC:

796

AN:

26108

East Asian (EAS)

AF:

0.00807

AC:

320

AN:

39666

South Asian (SAS)

AF:

0.0113

AC:

970

AN:

86216

European-Finnish (FIN)

AF:

0.0355

AC:

1891

AN:

53314

Middle Eastern (MID)

AF:

0.0664

AC:

365

AN:

5498

European-Non Finnish (NFE)

AF:

0.0386

AC:

42847

AN:

1111346

Other (OTH)

AF:

0.0367

AC:

2214

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

2587

5174

7761

10348

12935

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1540

3080

4620

6160

7700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0339

AC:

5104

AN:

150498

Hom.:

105

Cov.:

AF XY:

0.0346

AC XY:

2542

AN XY:

73384

show subpopulations

African (AFR)

AF:

0.0285

AC:

1166

AN:

40946

American (AMR)

AF:

0.0409

AC:

617

AN:

15104

Ashkenazi Jewish (ASJ)

AF:

0.0257

AC:

AN:

3464

East Asian (EAS)

AF:

0.00157

AC:

AN:

5094

South Asian (SAS)

AF:

0.0103

AC:

AN:

4750

European-Finnish (FIN)

AF:

0.0367

AC:

370

AN:

10086

Middle Eastern (MID)

AF:

0.102

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.0394

AC:

2669

AN:

67798

Other (OTH)

AF:

0.0436

AC:

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

240

480

721

961

1201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0381

Hom.:

208

Bravo

AF:

0.0335

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.0465

EpiControl

AF:

0.0475

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Arg205Arg in Exon 07 of OTOA: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 3.7% (263/7020) of Eu ropean American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs16972658). -

Oct 13, 2017

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. -

not provided

Benign:3

Dec 31, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.75

CADD

Benign

0.20

(source)

DANN

Benign

0.45

PhyloP100

-2.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over