dbSNP rs143890524: OTOA:p.Gln794Gln (chr16-21736341-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_144672.4(OTOA):c.2382G>A(p.Gln794Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00658 in 1,567,196 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0055 ( 0 hom. )

Consequence

OTOA
NM_144672.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.135

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 16-21736341-G-A is Benign according to our data. Variant chr16-21736341-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 506082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.135 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOA	NM_144672.4 link	c.2382G>A	p.Gln794Gln	synonymous_variant	Exon 22 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.2382G>A	p.Gln794Gln	synonymous_variant	Exon 22 of 29		NM_144672.4	ENSP00000496564.2		Q7RTW8-5

Frequencies

GnomAD3 genomes

AF:

0.0164

AC:

2436

AN:

148178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00306

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0596

Gnomad ASJ

AF:

0.00554

Gnomad EAS

AF:

0.180

Gnomad SAS

AF:

0.0200

Gnomad FIN

AF:

0.0447

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00224

Gnomad OTH

AF:

0.0222

GnomAD3 exomes

AF:

0.00223

AC:

506

AN:

227182

Hom.:

AF XY:

0.00194

AC XY:

242

AN XY:

124670

show subpopulations

Gnomad AFR exome

AF:

0.000186

Gnomad AMR exome

AF:

0.00655

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.0260

Gnomad SAS exome

AF:

0.000372

Gnomad FIN exome

AF:

0.00230

Gnomad NFE exome

AF:

0.0000622

Gnomad OTH exome

AF:

0.00106

GnomAD4 exome

AF:

0.00554

AC:

7861

AN:

1418908

Hom.:

Cov.:

AF XY:

0.00524

AC XY:

3704

AN XY:

706408

show subpopulations

Gnomad4 AFR exome

AF:

0.000420

Gnomad4 AMR exome

AF:

0.0507

Gnomad4 ASJ exome

AF:

0.00187

Gnomad4 EAS exome

AF:

0.170

Gnomad4 SAS exome

AF:

0.00252

Gnomad4 FIN exome

AF:

0.0129

Gnomad4 NFE exome

AF:

0.000493

Gnomad4 OTH exome

AF:

0.00678

GnomAD4 genome

AF:

0.0165

AC:

2445

AN:

148288

Hom.:

Cov.:

AF XY:

0.0193

AC XY:

1395

AN XY:

72128

show subpopulations

Gnomad4 AFR

AF:

0.00305

Gnomad4 AMR

AF:

0.0597

Gnomad4 ASJ

AF:

0.00554

Gnomad4 EAS

AF:

0.180

Gnomad4 SAS

AF:

0.0198

Gnomad4 FIN

AF:

0.0447

Gnomad4 NFE

AF:

0.00224

Gnomad4 OTH

AF:

0.0259

Alfa

AF:

0.00717

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 04, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Aug 23, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Gln794Gln in exon 21 of OTOA: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 21.59% (1708/7910) o f East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac. broadinstitute.org; dbSNP rs143890524). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.093

DANN

Benign

0.35

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

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