rs7112749

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001292063.2(OTOG):c.1940C>T(p.Thr647Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0403 in 1,550,308 control chromosomes in the GnomAD database, including 1,514 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 280 hom., cov: 32)

Exomes 𝑓: 0.039 ( 1234 hom. )

Consequence

OTOG
NM_001292063.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.63

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 18B
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics
nonsyndromic genetic hearing loss
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

OTOG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021283627).

BP6

Variant 11-17570375-C-T is Benign according to our data. Variant chr11-17570375-C-T is described in ClinVar as Benign. ClinVar VariationId is 226865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0889 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001292063.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOG	NM_001292063.2	MANE Select	c.1940C>T	p.Thr647Met	missense	Exon 17 of 56	NP_001278992.1	H9KVB3
	OTOG	NM_001277269.2		c.1976C>T	p.Thr659Met	missense	Exon 16 of 55	NP_001264198.1	Q6ZRI0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OTOG	ENST00000399397.6	TSL:5 MANE Select	c.1940C>T	p.Thr647Met	missense	Exon 17 of 56	ENSP00000382329.2	H9KVB3
OTOG	ENST00000399391.7	TSL:5	c.1976C>T	p.Thr659Met	missense	Exon 16 of 55	ENSP00000382323.2	Q6ZRI0-1
OTOG	ENST00000498332.5	TSL:5	n.1846C>T		non_coding_transcript_exon	Exon 16 of 16

Frequencies

GnomAD3 genomes

AF:

0.0522

AC:

7941

AN:

152040

Hom.:

278

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0914

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0572

Gnomad ASJ

AF:

0.0231

Gnomad EAS

AF:

0.00541

Gnomad SAS

AF:

0.0718

Gnomad FIN

AF:

0.0340

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0346

Gnomad OTH

AF:

0.0406

GnomAD2 exomes

AF:

0.0409

AC:

6087

AN:

148934

AF XY:

0.0420

show subpopulations

Gnomad AFR exome

AF:

0.0887

Gnomad AMR exome

AF:

0.0430

Gnomad ASJ exome

AF:

0.0276

Gnomad EAS exome

AF:

0.00464

Gnomad FIN exome

AF:

0.0330

Gnomad NFE exome

AF:

0.0325

Gnomad OTH exome

AF:

0.0372

GnomAD4 exome

AF:

0.0390

AC:

54536

AN:

1398150

Hom.:

1234

Cov.:

AF XY:

0.0398

AC XY:

27431

AN XY:

689598

show subpopulations

African (AFR)

AF:

0.0919

AC:

2904

AN:

31594

American (AMR)

AF:

0.0422

AC:

1505

AN:

35696

Ashkenazi Jewish (ASJ)

AF:

0.0266

AC:

669

AN:

25174

East Asian (EAS)

AF:

0.00853

AC:

305

AN:

35738

South Asian (SAS)

AF:

0.0740

AC:

5861

AN:

79222

European-Finnish (FIN)

AF:

0.0313

AC:

1508

AN:

48174

Middle Eastern (MID)

AF:

0.0168

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.0367

AC:

39546

AN:

1078862

Other (OTH)

AF:

0.0369

AC:

2142

AN:

57992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

2510

5021

7531

10042

12552

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1636

3272

4908

6544

8180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0523

AC:

7957

AN:

152158

Hom.:

280

Cov.:

AF XY:

0.0530

AC XY:

3941

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.0913

AC:

3791

AN:

41502

American (AMR)

AF:

0.0573

AC:

876

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0231

AC:

AN:

3470

East Asian (EAS)

AF:

0.00542

AC:

AN:

5168

South Asian (SAS)

AF:

0.0732

AC:

352

AN:

4812

European-Finnish (FIN)

AF:

0.0340

AC:

360

AN:

10592

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0346

AC:

2355

AN:

68002

Other (OTH)

AF:

0.0402

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

385

770

1154

1539

1924

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0384

Hom.:

432

Bravo

AF:

0.0520

TwinsUK

AF:

0.0448

AC:

166

ALSPAC

AF:

0.0368

AC:

142

ExAC

AF:

0.0445

AC:

961

Asia WGS

AF:

0.0450

AC:

156

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.043

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.85

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.45

PhyloP100

1.6

PrimateAI

Uncertain

0.50

PROVEAN

Benign

0.60

REVEL

Benign

0.031

Sift

Benign

0.23

Sift4G

Benign

0.36

Vest4

0.052

ClinPred

0.010

GERP RS

4.1

Varity_R

0.039

gMVP

0.39

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over