rs61731248

Positions:

chr11-17559106-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001292063.2(OTOG):c.1158G>A(p.Ala386=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,545,220 control chromosomes in the GnomAD database, including 727 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 271 hom., cov: 33)

Exomes 𝑓: 0.0074 ( 456 hom. )

Consequence

OTOG
NM_001292063.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.58

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 11-17559106-G-A is Benign according to our data. Variant chr11-17559106-G-A is described in ClinVar as [Benign]. Clinvar id is 226861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.58 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTOG	NM_001292063.2 linkuse as main transcript	c.1158G>A	p.Ala386=	synonymous_variant	11/56	ENST00000399397.6	NP_001278992.1
OTOG	NM_001277269.2 linkuse as main transcript	c.1194G>A	p.Ala398=	synonymous_variant	10/55		NP_001264198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTOG	ENST00000399397.6 linkuse as main transcript	c.1158G>A	p.Ala386=	synonymous_variant	11/56	5	NM_001292063.2	ENSP00000382329	P2
OTOG	ENST00000399391.7 linkuse as main transcript	c.1194G>A	p.Ala398=	synonymous_variant	10/55	5		ENSP00000382323	A2	Q6ZRI0-1
OTOG	ENST00000498332.5 linkuse as main transcript	n.1064G>A		non_coding_transcript_exon_variant	10/16	5

Frequencies

GnomAD3 genomes

AF:

0.0362

AC:

5515

AN:

152162

Hom.:

271

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0347

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.0955

Gnomad SAS

AF:

0.00745

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.0292

GnomAD3 exomes

AF:

0.0203

AC:

2901

AN:

142584

Hom.:

111

AF XY:

0.0174

AC XY:

1348

AN XY:

77348

show subpopulations

Gnomad AFR exome

AF:

0.105

Gnomad AMR exome

AF:

0.0372

Gnomad ASJ exome

AF:

0.00120

Gnomad EAS exome

AF:

0.0959

Gnomad SAS exome

AF:

0.00586

Gnomad FIN exome

AF:

0.0000868

Gnomad NFE exome

AF:

0.000946

Gnomad OTH exome

AF:

0.0121

GnomAD4 exome

AF:

0.00744

AC:

10364

AN:

1392940

Hom.:

456

Cov.:

AF XY:

0.00704

AC XY:

4839

AN XY:

687336

show subpopulations

Gnomad4 AFR exome

AF:

0.108

Gnomad4 AMR exome

AF:

0.0362

Gnomad4 ASJ exome

AF:

0.000755

Gnomad4 EAS exome

AF:

0.104

Gnomad4 SAS exome

AF:

0.00517

Gnomad4 FIN exome

AF:

0.0000932

Gnomad4 NFE exome

AF:

0.000627

Gnomad4 OTH exome

AF:

0.0133

GnomAD4 genome

AF:

0.0363

AC:

5524

AN:

152280

Hom.:

271

Cov.:

AF XY:

0.0371

AC XY:

2763

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.0347

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.0959

Gnomad4 SAS

AF:

0.00745

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.0289

Alfa

AF:

0.00902

Hom.:

Bravo

AF:

0.0449

Asia WGS

AF:

0.0390

AC:

137

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 31, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 03, 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	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	Ala398Ala in exon 10 of OTOG: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 11.5% (23/200) of Ha n Chinese chromosomes from a broad population by the 1000 Genomes Project (http: //www.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs61731248). -

OTOG-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

2.5

DANN

Benign

0.85

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