rs7111528

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.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. 15/21 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

Publications

20 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=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 VariationId is 226900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 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.5804C>T	p.Thr1935Met	missense	Exon 36 of 56	NP_001278992.1	H9KVB3
	OTOG	NM_001277269.2		c.5840C>T	p.Thr1947Met	missense	Exon 35 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.5804C>T	p.Thr1935Met	missense	Exon 36 of 56	ENSP00000382329.2	H9KVB3
OTOG	ENST00000399391.7	TSL:5	c.5840C>T	p.Thr1947Met	missense	Exon 35 of 55	ENSP00000382323.2	Q6ZRI0-1
OTOG	ENST00000342528.2	TSL:2	n.3142C>T		non_coding_transcript_exon	Exon 12 of 22

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

GnomAD2 exomes

AF:

0.346

AC:

50693

AN:

146524

AF XY:

0.355

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 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

African (AFR)

AF:

0.519

AC:

16401

AN:

31598

American (AMR)

AF:

0.227

AC:

8116

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.338

AC:

8515

AN:

25182

East Asian (EAS)

AF:

0.194

AC:

6919

AN:

35738

South Asian (SAS)

AF:

0.443

AC:

35092

AN:

79234

European-Finnish (FIN)

AF:

0.337

AC:

16230

AN:

48136

Middle Eastern (MID)

AF:

0.347

AC:

1977

AN:

5698

European-Non Finnish (NFE)

AF:

0.375

AC:

404169

AN:

1078946

Other (OTH)

AF:

0.366

AC:

21201

AN:

57996

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

23192

46383

69575

92766

115958

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13002

26004

39006

52008

65010

<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:

0.398

AC:

60504

AN:

152106

Hom.:

12623

Cov.:

AF XY:

0.395

AC XY:

29370

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.513

AC:

21302

AN:

41486

American (AMR)

AF:

0.302

AC:

4625

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.331

AC:

1149

AN:

3472

East Asian (EAS)

AF:

0.202

AC:

1044

AN:

5168

South Asian (SAS)

AF:

0.459

AC:

2207

AN:

4806

European-Finnish (FIN)

AF:

0.333

AC:

3531

AN:

10604

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.373

AC:

25353

AN:

67964

Other (OTH)

AF:

0.374

AC:

791

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1849

3697

5546

7394

9243

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

570

1140

1710

2280

2850

<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:

0.375

Hom.:

32369

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.7

(source)

DANN

Benign

0.46

DEOGEN2

Benign

0.056

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0059

LIST_S2

Benign

0.47

MetaRNN

Benign

0.000039

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.29

PhyloP100

-0.45

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.5

REVEL

Benign

0.0050

Sift

Benign

0.27

Sift4G

Benign

0.12

Vest4

0.059

ClinPred

0.0036

GERP RS

-0.81

Varity_R

0.017

gMVP

0.27

Mutation Taster

=100/0

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