16-21678558-T-A

Position:

chr16-21678558-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_144672.4(OTOA):c.44T>A(p.Phe15Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0308 in 1,613,658 control chromosomes in the GnomAD database, including 4,331 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.051 ( 492 hom., cov: 31)

Exomes 𝑓: 0.029 ( 3839 hom. )

Consequence

OTOA
NM_144672.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.42

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003518194).

BP6

Variant 16-21678558-T-A is Benign according to our data. Variant chr16-21678558-T-A is described in ClinVar as [Benign]. Clinvar id is 47954.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTOA	NM_144672.4 linkuse as main transcript	c.44T>A	p.Phe15Tyr	missense_variant	2/29	ENST00000646100.2	NP_653273.3	Q05BM7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OTOA	ENST00000646100.2 linkuse as main transcript	c.44T>A	p.Phe15Tyr	missense_variant	2/29		NM_144672.4	ENSP00000496564.2	Q7RTW8-5
OTOA	ENST00000388958.8 linkuse as main transcript	c.44T>A	p.Phe15Tyr	missense_variant	1/28	1		ENSP00000373610.3	Q7RTW8-5
OTOA	ENST00000286149.8 linkuse as main transcript	c.44T>A	p.Phe15Tyr	missense_variant	1/28	5		ENSP00000286149.4	Q7RTW8-1
OTOA	ENST00000647277.1 linkuse as main transcript	n.44T>A		non_coding_transcript_exon_variant	2/29			ENSP00000495594.1	A0A2R8YG28

Frequencies

GnomAD3 genomes

AF:

0.0511

AC:

7760

AN:

151944

Hom.:

485

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0806

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.0328

Gnomad EAS

AF:

0.265

Gnomad SAS

AF:

0.0506

Gnomad FIN

AF:

0.0109

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00950

Gnomad OTH

AF:

0.0567

GnomAD3 exomes

AF:

0.0681

AC:

17125

AN:

251456

Hom.:

1808

AF XY:

0.0585

AC XY:

7951

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.0789

Gnomad AMR exome

AF:

0.227

Gnomad ASJ exome

AF:

0.0308

Gnomad EAS exome

AF:

0.247

Gnomad SAS exome

AF:

0.0412

Gnomad FIN exome

AF:

0.0129

Gnomad NFE exome

AF:

0.0114

Gnomad OTH exome

AF:

0.0484

GnomAD4 exome

AF:

0.0287

AC:

41897

AN:

1461596

Hom.:

3839

Cov.:

AF XY:

0.0281

AC XY:

20448

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.0787

Gnomad4 AMR exome

AF:

0.214

Gnomad4 ASJ exome

AF:

0.0302

Gnomad4 EAS exome

AF:

0.322

Gnomad4 SAS exome

AF:

0.0396

Gnomad4 FIN exome

AF:

0.0137

Gnomad4 NFE exome

AF:

0.00866

Gnomad4 OTH exome

AF:

0.0348

GnomAD4 genome

AF:

0.0512

AC:

7785

AN:

152062

Hom.:

492

Cov.:

AF XY:

0.0537

AC XY:

3992

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0808

Gnomad4 AMR

AF:

0.120

Gnomad4 ASJ

AF:

0.0328

Gnomad4 EAS

AF:

0.265

Gnomad4 SAS

AF:

0.0502

Gnomad4 FIN

AF:

0.0109

Gnomad4 NFE

AF:

0.00948

Gnomad4 OTH

AF:

0.0551

Alfa

AF:

0.0253

Hom.:

226

Bravo

AF:

0.0658

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.0780

AC:

343

ESP6500EA

AF:

0.0110

AC:

ExAC

AF:

0.0623

AC:

7569

Asia WGS

AF:

0.132

AC:

456

AN:

3478

EpiCase

AF:

0.0118

EpiControl

AF:

0.0104

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	Phe15Tyr in Exon 01 of OTOA: This variant is not expected to have clinical signi ficance because it has been identified in 8.2% (305/3738) of African American ch romosomes from a broad population by the NHLBI Exome Sequencing Project (http:// evs.gs.washington.edu/EVS; dbSNP rs78970023). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 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	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

.;T;.

Eigen

Benign

-0.085

Eigen_PC

Benign

-0.082

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.46

.;T;T

MetaRNN

Benign

0.0035

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;M;M

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.67

.;N;N

REVEL

Benign

0.17

Sift

Benign

0.030

.;D;D

Sift4G

Uncertain

0.042

.;D;D

Vest4

0.12, 0.17

MPC

0.47

ClinPred

0.021

GERP RS

4.7

Varity_R

0.084

gMVP

0.11

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