NM_001292063.2:c.3188G>A

Variant names:

Variant summary

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

The NM_001292063.2(OTOG):c.3188G>A(p.Arg1063Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,548,944 control chromosomes in the GnomAD database, including 19,994 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1605 hom., cov: 32)

Exomes 𝑓: 0.16 ( 18389 hom. )

Consequence

OTOG
NM_001292063.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0500

Variant links:

Genes affected

OTOG (HGNC:8516): (otogelin) The protein encoded by this gene is a component of the acellular membranes of the inner ear. Disruption of the orthologous mouse gene shows that it plays a role in auditory and vestibular functions. It is involved in fibrillar network organization, the anchoring of otoconial membranes and cupulae to the neuroepithelia, and likely in sound stimulation resistance. Mutations in this gene cause autosomal recessive nonsyndromic deafness, type 18B. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2014]

OTOG 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=0.0037749708).

BP6

Variant 11-17593656-G-A is Benign according to our data. Variant chr11-17593656-G-A is described in ClinVar as [Benign]. Clinvar id is 226879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17593656-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOG	NM_001292063.2 link	c.3188G>A	p.Arg1063Gln	missense_variant	Exon 27 of 56	ENST00000399397.6	NP_001278992.1	H9KVB3
OTOG	NM_001277269.2 link	c.3224G>A	p.Arg1075Gln	missense_variant	Exon 26 of 55		NP_001264198.1	Q6ZRI0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OTOG	ENST00000399397.6 link	c.3188G>A	p.Arg1063Gln	missense_variant	Exon 27 of 56	5	NM_001292063.2	ENSP00000382329.2	H9KVB3
OTOG	ENST00000399391.7 link	c.3224G>A	p.Arg1075Gln	missense_variant	Exon 26 of 55	5		ENSP00000382323.2	Q6ZRI0-1
OTOG	ENST00000342528.2 link	n.553G>A		non_coding_transcript_exon_variant	Exon 4 of 22	2

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20776

AN:

152048

Hom.:

1605

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0875

Gnomad AMI

AF:

0.330

Gnomad AMR

AF:

0.0972

Gnomad ASJ

AF:

0.189

Gnomad EAS

AF:

0.204

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.127

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.162

Gnomad OTH

AF:

0.139

GnomAD3 exomes

AF:

0.151

AC:

22323

AN:

147754

Hom.:

1877

AF XY:

0.156

AC XY:

12456

AN XY:

79652

show subpopulations

Gnomad AFR exome

AF:

0.0878

Gnomad AMR exome

AF:

0.0767

Gnomad ASJ exome

AF:

0.186

Gnomad EAS exome

AF:

0.224

Gnomad SAS exome

AF:

0.191

Gnomad FIN exome

AF:

0.131

Gnomad NFE exome

AF:

0.162

Gnomad OTH exome

AF:

0.151

GnomAD4 exome

AF:

0.160

AC:

223638

AN:

1396778

Hom.:

18389

Cov.:

AF XY:

0.162

AC XY:

111547

AN XY:

688938

show subpopulations

Gnomad4 AFR exome

AF:

0.0901

Gnomad4 AMR exome

AF:

0.0797

Gnomad4 ASJ exome

AF:

0.184

Gnomad4 EAS exome

AF:

0.191

Gnomad4 SAS exome

AF:

0.190

Gnomad4 FIN exome

AF:

0.132

Gnomad4 NFE exome

AF:

0.162

Gnomad4 OTH exome

AF:

0.162

GnomAD4 genome

AF:

0.137

AC:

20784

AN:

152166

Hom.:

1605

Cov.:

AF XY:

0.136

AC XY:

10143

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0876

Gnomad4 AMR

AF:

0.0970

Gnomad4 ASJ

AF:

0.189

Gnomad4 EAS

AF:

0.205

Gnomad4 SAS

AF:

0.200

Gnomad4 FIN

AF:

0.127

Gnomad4 NFE

AF:

0.162

Gnomad4 OTH

AF:

0.138

Alfa

AF:

0.150

Hom.:

2916

Bravo

AF:

0.130

TwinsUK

AF:

0.156

AC:

579

ALSPAC

AF:

0.156

AC:

600

ExAC

AF:

0.138

AC:

3142

Asia WGS

AF:

0.206

AC:

716

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

May 09, 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. -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Arg1075Gln in exon 26 of OTOG: This variant is not expected to have clinical sig nificance because it has been identified in 21.5% (43/200) of Han Chinese chromo somes from a broad population by the 1000 Genomes Project (http://www.ncbi.nlm.n ih.gov/projects/SNP; dbSNP rs11024333). -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 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

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

9.5

DANN

Benign

0.70

DEOGEN2

Benign

0.022

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.77

T;T

MetaRNN

Benign

0.0038

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.62

N;.

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.29

N;.

REVEL

Benign

0.076

Sift

Benign

0.30

T;.

Sift4G

Benign

1.0

T;T

Vest4

0.069

ClinPred

0.0024

GERP RS

-3.4

Varity_R

0.043

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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