rs116947228

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001292063.2(OTOG):c.3674G>A(p.Arg1225His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00447 in 1,549,584 control chromosomes in the GnomAD database, including 200 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0054 ( 31 hom., cov: 33)

Exomes 𝑓: 0.0044 ( 169 hom. )

Consequence

OTOG
NM_001292063.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.718

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023708344).

BP6

Variant 11-17596999-G-A is Benign according to our data. Variant chr11-17596999-G-A is described in ClinVar as [Benign]. Clinvar id is 226890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17596999-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOG	NM_001292063.2 link	c.3674G>A	p.Arg1225His	missense_variant	Exon 30 of 56	ENST00000399397.6	NP_001278992.1	H9KVB3
OTOG	NM_001277269.2 link	c.3710G>A	p.Arg1237His	missense_variant	Exon 29 of 55		NP_001264198.1	Q6ZRI0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OTOG	ENST00000399397.6 link	c.3674G>A	p.Arg1225His	missense_variant	Exon 30 of 56	5	NM_001292063.2	ENSP00000382329.2	H9KVB3
OTOG	ENST00000399391.7 link	c.3710G>A	p.Arg1237His	missense_variant	Exon 29 of 55	5		ENSP00000382323.2	Q6ZRI0-1
OTOG	ENST00000342528.2 link	n.1039G>A		non_coding_transcript_exon_variant	Exon 7 of 22	2

Frequencies

GnomAD3 genomes

AF:

0.00543

AC:

826

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.0922

Gnomad SAS

AF:

0.00456

Gnomad FIN

AF:

0.0120

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00185

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00837

AC:

1242

AN:

148472

Hom.:

AF XY:

0.00808

AC XY:

646

AN XY:

79994

show subpopulations

Gnomad AFR exome

AF:

0.00133

Gnomad AMR exome

AF:

0.000367

Gnomad ASJ exome

AF:

0.00144

Gnomad EAS exome

AF:

0.0840

Gnomad SAS exome

AF:

0.00253

Gnomad FIN exome

AF:

0.00819

Gnomad NFE exome

AF:

0.00176

Gnomad OTH exome

AF:

0.00419

GnomAD4 exome

AF:

0.00436

AC:

6099

AN:

1397336

Hom.:

169

Cov.:

AF XY:

0.00427

AC XY:

2946

AN XY:

689234

show subpopulations

Gnomad4 AFR exome

AF:

0.000506

Gnomad4 AMR exome

AF:

0.000420

Gnomad4 ASJ exome

AF:

0.00135

Gnomad4 EAS exome

AF:

0.0908

Gnomad4 SAS exome

AF:

0.00249

Gnomad4 FIN exome

AF:

0.00855

Gnomad4 NFE exome

AF:

0.00167

Gnomad4 OTH exome

AF:

0.00647

GnomAD4 genome

AF:

0.00541

AC:

824

AN:

152248

Hom.:

Cov.:

AF XY:

0.00661

AC XY:

492

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.0919

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.0120

Gnomad4 NFE

AF:

0.00185

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00196

Hom.:

Bravo

AF:

0.00472

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.00397

AC:

Asia WGS

AF:

0.0310

AC:

109

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Arg1237His in exon 29 of OTOG: This variant is not expected to have clinical sig nificance because it has been identified in 10.1% (18/178) of Japanese chromosom es from a broad population by the 1000 Genomes Project (http://www.ncbi.nlm.nih. gov/projects/SNP; dbSNP rs116947228). -

Aug 22, 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:1

Jan 29, 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

0.069

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.047

T;.

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.57

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.76

T;T

MetaRNN

Benign

0.0024

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;.

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.7

N;.

REVEL

Benign

0.090

Sift

Benign

0.21

T;.

Sift4G

Uncertain

0.0080

D;D

Vest4

0.16

MVP

0.24

ClinPred

0.0037

GERP RS

1.8

Varity_R

0.041

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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