rs11836060

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_001378609.3(OTOGL):c.5984G>A(p.Arg1995Gln) variant causes a missense change. The variant allele was found at a frequency of 0.189 in 1,595,220 control chromosomes in the GnomAD database, including 30,055 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2731 hom., cov: 31)

Exomes 𝑓: 0.19 ( 27324 hom. )

Consequence

OTOGL
NM_001378609.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.89

Variant links:

Genes affected

OTOGL (HGNC:26901): (otogelin like) The protein encoded by this gene belongs to the otogelin family. This gene is expressed in the inner ear of vertebrates with the highest level of expression seen at the embryonic stage and lowest in adult. Knockdown studies in zebrafish suggest that this gene is essential for normal inner ear function. Mutations in this gene are associated with autosomal recessive deafness. [provided by RefSeq, Dec 2012]

OTOGL 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=0.0010064244).

BP6

Variant 12-80356879-G-A is Benign according to our data. Variant chr12-80356879-G-A is described in ClinVar as [Benign]. Clinvar id is 226962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-80356879-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOGL	NM_001378609.3 link	c.5984G>A	p.Arg1995Gln	missense_variant	Exon 49 of 59	ENST00000547103.7	NP_001365538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTOGL	ENST00000547103.7 link	c.5984G>A	p.Arg1995Gln	missense_variant	Exon 49 of 59	5	NM_001378609.3	ENSP00000447211.2		Q3ZCN5

Frequencies

GnomAD3 genomes

AF:

0.184

AC:

27972

AN:

151668

Hom.:

2730

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.284

Gnomad AMR

AF:

0.216

Gnomad ASJ

AF:

0.187

Gnomad EAS

AF:

0.0478

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.107

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.198

Gnomad OTH

AF:

0.190

GnomAD3 exomes

AF:

0.174

AC:

41129

AN:

236718

Hom.:

3972

AF XY:

0.177

AC XY:

22731

AN XY:

128616

show subpopulations

Gnomad AFR exome

AF:

0.172

Gnomad AMR exome

AF:

0.194

Gnomad ASJ exome

AF:

0.188

Gnomad EAS exome

AF:

0.0399

Gnomad SAS exome

AF:

0.207

Gnomad FIN exome

AF:

0.103

Gnomad NFE exome

AF:

0.193

Gnomad OTH exome

AF:

0.182

GnomAD4 exome

AF:

0.190

AC:

274297

AN:

1443436

Hom.:

27324

Cov.:

AF XY:

0.191

AC XY:

136974

AN XY:

717914

show subpopulations

Gnomad4 AFR exome

AF:

0.172

Gnomad4 AMR exome

AF:

0.200

Gnomad4 ASJ exome

AF:

0.188

Gnomad4 EAS exome

AF:

0.0355

Gnomad4 SAS exome

AF:

0.204

Gnomad4 FIN exome

AF:

0.110

Gnomad4 NFE exome

AF:

0.199

Gnomad4 OTH exome

AF:

0.186

GnomAD4 genome

AF:

0.184

AC:

27974

AN:

151784

Hom.:

2731

Cov.:

AF XY:

0.181

AC XY:

13441

AN XY:

74164

show subpopulations

Gnomad4 AFR

AF:

0.180

Gnomad4 AMR

AF:

0.216

Gnomad4 ASJ

AF:

0.187

Gnomad4 EAS

AF:

0.0480

Gnomad4 SAS

AF:

0.215

Gnomad4 FIN

AF:

0.107

Gnomad4 NFE

AF:

0.198

Gnomad4 OTH

AF:

0.188

Alfa

AF:

0.190

Hom.:

5785

Bravo

AF:

0.192

TwinsUK

AF:

0.193

AC:

714

ALSPAC

AF:

0.199

AC:

767

ESP6500AA

AF:

0.187

AC:

823

ESP6500EA

AF:

0.197

AC:

1690

ExAC

AF:

0.182

AC:

22088

Asia WGS

AF:

0.140

AC:

484

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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

Arg1986Gln in exon 48 of OTOGL: This variant is not expected to have clinical si gnificance because it has been identified in 19.7% (1690/8600) of European Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs11836060). -

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

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.36

T;.;T

MetaRNN

Benign

0.0010

T;T;T

MetaSVM

Benign

-0.97

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.6

.;.;N

REVEL

Benign

0.066

Sift

Benign

0.34

.;.;T

Sift4G

Benign

0.27

.;.;T

Vest4

0.061

MPC

0.023

ClinPred

0.021

GERP RS

4.1

gMVP

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