11-17611104-C-T

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.5804C>T(p.Thr1935Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 1,550,336 control chromosomes in the GnomAD database, including 110,870 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 0.40 ( 12623 hom., cov: 32)

Exomes 𝑓: 0.37 ( 98247 hom. )

Consequence

OTOG
NM_001292063.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.448

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=3.946672E-5).

BP6

Variant 11-17611104-C-T is Benign according to our data. Variant chr11-17611104-C-T is described in ClinVar as [Benign]. Clinvar id is 226900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17611104-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOG	NM_001292063.2 link	c.5804C>T	p.Thr1935Met	missense_variant	Exon 36 of 56	ENST00000399397.6	NP_001278992.1	H9KVB3
OTOG	NM_001277269.2 link	c.5840C>T	p.Thr1947Met	missense_variant	Exon 35 of 55		NP_001264198.1	Q6ZRI0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OTOG	ENST00000399397.6 link	c.5804C>T	p.Thr1935Met	missense_variant	Exon 36 of 56	5	NM_001292063.2	ENSP00000382329.2	H9KVB3
OTOG	ENST00000399391.7 link	c.5840C>T	p.Thr1947Met	missense_variant	Exon 35 of 55	5		ENSP00000382323.2	Q6ZRI0-1
OTOG	ENST00000342528.2 link	n.3142C>T		non_coding_transcript_exon_variant	Exon 12 of 22	2

Frequencies

GnomAD3 genomes

AF:

0.398

AC:

60435

AN:

151988

Hom.:

12598

Cov.:

show subpopulations

Gnomad AFR

AF:

0.513

Gnomad AMI

AF:

0.440

Gnomad AMR

AF:

0.303

Gnomad ASJ

AF:

0.331

Gnomad EAS

AF:

0.201

Gnomad SAS

AF:

0.460

Gnomad FIN

AF:

0.333

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.373

Gnomad OTH

AF:

0.375

GnomAD3 exomes

AF:

0.346

AC:

50693

AN:

146524

Hom.:

9387

AF XY:

0.355

AC XY:

28040

AN XY:

78974

show subpopulations

Gnomad AFR exome

AF:

0.519

Gnomad AMR exome

AF:

0.217

Gnomad ASJ exome

AF:

0.342

Gnomad EAS exome

AF:

0.212

Gnomad SAS exome

AF:

0.445

Gnomad FIN exome

AF:

0.341

Gnomad NFE exome

AF:

0.373

Gnomad OTH exome

AF:

0.330

GnomAD4 exome

AF:

0.371

AC:

518620

AN:

1398230

Hom.:

98247

Cov.:

AF XY:

0.373

AC XY:

257064

AN XY:

689634

show subpopulations

Gnomad4 AFR exome

AF:

0.519

Gnomad4 AMR exome

AF:

0.227

Gnomad4 ASJ exome

AF:

0.338

Gnomad4 EAS exome

AF:

0.194

Gnomad4 SAS exome

AF:

0.443

Gnomad4 FIN exome

AF:

0.337

Gnomad4 NFE exome

AF:

0.375

Gnomad4 OTH exome

AF:

0.366

GnomAD4 genome

AF:

0.398

AC:

60504

AN:

152106

Hom.:

12623

Cov.:

AF XY:

0.395

AC XY:

29370

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.513

Gnomad4 AMR

AF:

0.302

Gnomad4 ASJ

AF:

0.331

Gnomad4 EAS

AF:

0.202

Gnomad4 SAS

AF:

0.459

Gnomad4 FIN

AF:

0.333

Gnomad4 NFE

AF:

0.373

Gnomad4 OTH

AF:

0.374

Alfa

AF:

0.365

Hom.:

13851

Bravo

AF:

0.393

TwinsUK

AF:

0.376

AC:

1396

ALSPAC

AF:

0.366

AC:

1411

ExAC

AF:

0.358

AC:

7290

Asia WGS

AF:

0.366

AC:

1273

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

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Thr1947Met in exon 35 of OTOG: This variant is not expected to have clinical sig nificance because it has been identified in 58.2% (113/194) of Luhya (Kenyan) ch romosomes from a broad population by the 1000 Genomes Project (http://www.ncbi.n lm.nih.gov/projects/SNP; dbSNP rs7111528). -

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. -

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

0.070

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.7

DANN

Benign

0.46

DEOGEN2

Benign

0.056

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0059

LIST_S2

Benign

0.47

T;T

MetaRNN

Benign

0.000039

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.29

N;.

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.5

N;.

REVEL

Benign

0.0050

Sift

Benign

0.27

T;.

Sift4G

Benign

0.12

T;T

Vest4

0.059

ClinPred

0.0036

GERP RS

-0.81

Varity_R

0.017

gMVP

0.27

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