Variant 16-21730867-G-A details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.08

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:

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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 linkuse as main transcript	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 linkuse as main transcript	c.2238G>A	p.Thr746=	synonymous_variant	21/29		NM_144672.4	P2	Q7RTW8-5

Frequencies

GnomAD3 genomes

AF:

0.0145

AC:

2126

AN:

146584

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00183

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0460

Gnomad ASJ

AF:

0.00443

Gnomad EAS

AF:

0.171

Gnomad SAS

AF:

0.0187

Gnomad FIN

AF:

0.0465

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00239

Gnomad OTH

AF:

0.0186

GnomAD3 exomes

AF:

0.0533

AC:

12804

AN:

240440

Hom.:

346

AF XY:

0.0454

AC XY:

5897

AN XY:

129832

show subpopulations

Gnomad AFR exome

AF:

0.00402

Gnomad AMR exome

AF:

0.182

Gnomad ASJ exome

AF:

0.0114

Gnomad EAS exome

AF:

0.234

Gnomad SAS exome

AF:

0.0204

Gnomad FIN exome

AF:

0.0755

Gnomad NFE exome

AF:

0.00625

Gnomad OTH exome

AF:

0.0352

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0165

AC:

23282

AN:

1410698

Hom.:

421

Cov.:

AF XY:

0.0159

AC XY:

11157

AN XY:

702380

show subpopulations

Gnomad4 AFR exome

AF:

0.00180

Gnomad4 AMR exome

AF:

0.163

Gnomad4 ASJ exome

AF:

0.00847

Gnomad4 EAS exome

AF:

0.250

Gnomad4 SAS exome

AF:

0.0200

Gnomad4 FIN exome

AF:

0.0568

Gnomad4 NFE exome

AF:

0.00230

Gnomad4 OTH exome

AF:

0.0234

GnomAD4 genome

AF:

0.0146

AC:

2136

AN:

146692

Hom.:

Cov.:

AF XY:

0.0175

AC XY:

1249

AN XY:

71226

show subpopulations

Gnomad4 AFR

AF:

0.00182

Gnomad4 AMR

AF:

0.0460

Gnomad4 ASJ

AF:

0.00443

Gnomad4 EAS

AF:

0.171

Gnomad4 SAS

AF:

0.0187

Gnomad4 FIN

AF:

0.0465

Gnomad4 NFE

AF:

0.00239

Gnomad4 OTH

AF:

0.0225

Alfa

AF:

0.00802

Hom.:

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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.22

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.21

Position offset: -30

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