rs10862089

Variant names:

Variant summary

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

The NM_001378609.3(OTOGL):c.3333G>T(p.Gln1111His) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.08 in 1,521,884 control chromosomes in the GnomAD database, including 5,234 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.080 ( 542 hom., cov: 33)

Exomes 𝑓: 0.080 ( 4692 hom. )

Consequence

OTOGL
NM_001378609.3 missense, splice_region

Scores

Splicing: ADA: 0.7123

Clinical Significance

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

Conservation

PhyloP100: 5.06

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=0.0030183494).

BP6

Variant 12-80305695-G-T is Benign according to our data. Variant chr12-80305695-G-T is described in ClinVar as [Benign]. Clinvar id is 226940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-80305695-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOGL	NM_001378609.3 link	c.3333G>T	p.Gln1111His	missense_variant, splice_region_variant	Exon 29 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.3333G>T	p.Gln1111His	missense_variant, splice_region_variant	Exon 29 of 59	5	NM_001378609.3	ENSP00000447211.2		Q3ZCN5
OTOGL	ENST00000646859.1 link	c.3198G>T	p.Gln1066His	missense_variant, splice_region_variant	Exon 33 of 63			ENSP00000496036.1		A0A2R8YF04

Frequencies

GnomAD3 genomes

AF:

0.0800

AC:

12163

AN:

151952

Hom.:

539

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0725

Gnomad AMI

AF:

0.0584

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.0657

Gnomad EAS

AF:

0.0453

Gnomad SAS

AF:

0.136

Gnomad FIN

AF:

0.0589

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0801

Gnomad OTH

AF:

0.0789

GnomAD3 exomes

AF:

0.0894

AC:

16728

AN:

187164

Hom.:

846

AF XY:

0.0900

AC XY:

9376

AN XY:

104202

show subpopulations

Gnomad AFR exome

AF:

0.0732

Gnomad AMR exome

AF:

0.146

Gnomad ASJ exome

AF:

0.0658

Gnomad EAS exome

AF:

0.0428

Gnomad SAS exome

AF:

0.137

Gnomad FIN exome

AF:

0.0597

Gnomad NFE exome

AF:

0.0812

Gnomad OTH exome

AF:

0.0820

GnomAD4 exome

AF:

0.0800

AC:

109583

AN:

1369814

Hom.:

4692

Cov.:

AF XY:

0.0815

AC XY:

55461

AN XY:

680408

show subpopulations

Gnomad4 AFR exome

AF:

0.0739

Gnomad4 AMR exome

AF:

0.142

Gnomad4 ASJ exome

AF:

0.0624

Gnomad4 EAS exome

AF:

0.0359

Gnomad4 SAS exome

AF:

0.132

Gnomad4 FIN exome

AF:

0.0630

Gnomad4 NFE exome

AF:

0.0778

Gnomad4 OTH exome

AF:

0.0772

GnomAD4 genome

AF:

0.0800

AC:

12166

AN:

152070

Hom.:

542

Cov.:

AF XY:

0.0802

AC XY:

5961

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0725

Gnomad4 AMR

AF:

0.113

Gnomad4 ASJ

AF:

0.0657

Gnomad4 EAS

AF:

0.0454

Gnomad4 SAS

AF:

0.136

Gnomad4 FIN

AF:

0.0589

Gnomad4 NFE

AF:

0.0801

Gnomad4 OTH

AF:

0.0781

Alfa

AF:

0.0799

Hom.:

1012

Bravo

AF:

0.0819

TwinsUK

AF:

0.0707

AC:

262

ALSPAC

AF:

0.0776

AC:

299

ESP6500AA

AF:

0.0722

AC:

261

ESP6500EA

AF:

0.0767

AC:

624

ExAC

AF:

0.0884

AC:

10504

Asia WGS

AF:

0.0950

AC:

331

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

Gln1102His in exon 28 of OTOGL: This variant is not expected to have clinical si gnificance because it has been identified in 7.7% (624/8136) of European America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs10862089). -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.84

T;.;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.0030

T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.6

.;.;D

REVEL

Benign

0.15

Sift

Uncertain

0.0040

.;.;D

Sift4G

Uncertain

0.0020

.;.;D

Vest4

0.37

MutPred

0.60

.;.;Gain of catalytic residue at Q1102 (P = 0.0068);

MPC

0.10

ClinPred

0.014

GERP RS

3.1

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.71

dbscSNV1_RF

Benign

0.24

SpliceAI score (max)

0.48

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.48

Position offset: 0

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