11-17594108-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.3350C>T(p.Pro1117Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00757 in 1,550,440 control chromosomes in the GnomAD database, including 736 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 418 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 318 hom. )

Consequence

OTOG
NM_001292063.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 5.63

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=0.002730459).

BP6

Variant 11-17594108-C-T is Benign according to our data. Variant chr11-17594108-C-T is described in ClinVar as [Benign]. Clinvar id is 226884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOG	NM_001292063.2 link	c.3350C>T	p.Pro1117Leu	missense_variant	Exon 28 of 56	ENST00000399397.6	NP_001278992.1	H9KVB3
OTOG	NM_001277269.2 link	c.3386C>T	p.Pro1129Leu	missense_variant	Exon 27 of 55		NP_001264198.1	Q6ZRI0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OTOG	ENST00000399397.6 link	c.3350C>T	p.Pro1117Leu	missense_variant	Exon 28 of 56	5	NM_001292063.2	ENSP00000382329.2	H9KVB3
OTOG	ENST00000399391.7 link	c.3386C>T	p.Pro1129Leu	missense_variant	Exon 27 of 55	5		ENSP00000382323.2	Q6ZRI0-1
OTOG	ENST00000342528.2 link	n.715C>T		non_coding_transcript_exon_variant	Exon 5 of 22	2

Frequencies

GnomAD3 genomes

AF:

0.0389

AC:

5921

AN:

152080

Hom.:

418

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0145

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.000779

Gnomad OTH

AF:

0.0335

GnomAD3 exomes

AF:

0.00824

AC:

1230

AN:

149206

Hom.:

AF XY:

0.00658

AC XY:

529

AN XY:

80368

show subpopulations

Gnomad AFR exome

AF:

0.142

Gnomad AMR exome

AF:

0.00745

Gnomad ASJ exome

AF:

0.00131

Gnomad EAS exome

AF:

0.0000927

Gnomad SAS exome

AF:

0.000355

Gnomad FIN exome

AF:

0.0000595

Gnomad NFE exome

AF:

0.000654

Gnomad OTH exome

AF:

0.00765

GnomAD4 exome

AF:

0.00416

AC:

5816

AN:

1398242

Hom.:

318

Cov.:

AF XY:

0.00368

AC XY:

2539

AN XY:

689648

show subpopulations

Gnomad4 AFR exome

AF:

0.138

Gnomad4 AMR exome

AF:

0.00815

Gnomad4 ASJ exome

AF:

0.000755

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000517

Gnomad4 FIN exome

AF:

0.0000208

Gnomad4 NFE exome

AF:

0.000468

Gnomad4 OTH exome

AF:

0.00940

GnomAD4 genome

AF:

0.0389

AC:

5927

AN:

152198

Hom.:

418

Cov.:

AF XY:

0.0375

AC XY:

2788

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.134

Gnomad4 AMR

AF:

0.0145

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000779

Gnomad4 OTH

AF:

0.0331

Alfa

AF:

0.0108

Hom.:

154

Bravo

AF:

0.0450

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ExAC

AF:

0.00710

AC:

144

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 23, 2018

Athena Diagnostics

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

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Oct 05, 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

Pro1129Leu in exon 27 of OTOG: This variant is not expected to have clinical sig nificance because it has been identified in 15.5% (30/194) of Luhya (Kenyan) chr omosomes from a broad population by the 1000 Genomes Project (http://www.ncbi.nl m.nih.gov/projects/SNP; dbSNP rs7936354). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

T;.

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.94

D;D

MetaRNN

Benign

0.0027

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.4

M;.

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-4.3

D;.

REVEL

Uncertain

0.48

Sift

Uncertain

0.0050

D;.

Sift4G

Uncertain

0.0060

D;D

Vest4

0.56

MVP

0.74

ClinPred

0.019

GERP RS

4.6

Varity_R

0.32

gMVP

0.82

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