rs1551122

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_001378609.3(OTOGL):c.6737A>G(p.Asn2246Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.608 in 1,538,726 control chromosomes in the GnomAD database, including 294,099 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 22244 hom., cov: 32)

Exomes 𝑓: 0.62 ( 271855 hom. )

Consequence

OTOGL
NM_001378609.3 missense, splice_region

Scores

Splicing: ADA: 0.8902

Clinical Significance

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

Conservation

PhyloP100: 4.50

Publications

25 publications found

Variant links:

Genes affected

OTOGL (HGNC:26901): (otogelin like) The protein encoded by this gene belongs to the otogelin family. This gene is expressed in the inner ear of vertebrates with the highest level of expression seen at the embryonic stage and lowest in adult. Knockdown studies in zebrafish suggest that this gene is essential for normal inner ear function. Mutations in this gene are associated with autosomal recessive deafness. [provided by RefSeq, Dec 2012]

OTOGL Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 84B
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
nonsyndromic genetic hearing loss
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

OTOGL 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=4.559077E-6).

BP6

Variant 12-80372020-A-G is Benign according to our data. Variant chr12-80372020-A-G is described in ClinVar as Benign. ClinVar VariationId is 226972.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOGL	NM_001378609.3 link	c.6737A>G	p.Asn2246Ser	missense_variant, splice_region_variant	Exon 57 of 59	ENST00000547103.7	NP_001365538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTOGL	ENST00000547103.7 link	c.6737A>G	p.Asn2246Ser	missense_variant, splice_region_variant	Exon 57 of 59	5	NM_001378609.3	ENSP00000447211.2		Q3ZCN5

Frequencies

GnomAD3 genomes

AF:

0.503

AC:

76353

AN:

151816

Hom.:

22245

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.488

Gnomad AMR

AF:

0.474

Gnomad ASJ

AF:

0.635

Gnomad EAS

AF:

0.724

Gnomad SAS

AF:

0.626

Gnomad FIN

AF:

0.685

Gnomad MID

AF:

0.545

Gnomad NFE

AF:

0.637

Gnomad OTH

AF:

0.545

GnomAD2 exomes

AF:

0.581

AC:

122147

AN:

210322

AF XY:

0.597

show subpopulations

Gnomad AFR exome

AF:

0.172

Gnomad AMR exome

AF:

0.383

Gnomad ASJ exome

AF:

0.633

Gnomad EAS exome

AF:

0.697

Gnomad FIN exome

AF:

0.686

Gnomad NFE exome

AF:

0.636

Gnomad OTH exome

AF:

0.589

GnomAD4 exome

AF:

0.619

AC:

859074

AN:

1386792

Hom.:

271855

Cov.:

AF XY:

0.622

AC XY:

429197

AN XY:

690076

show subpopulations

African (AFR)

AF:

0.170

AC:

5302

AN:

31220

American (AMR)

AF:

0.405

AC:

15245

AN:

37622

Ashkenazi Jewish (ASJ)

AF:

0.628

AC:

15721

AN:

25014

East Asian (EAS)

AF:

0.725

AC:

26217

AN:

36150

South Asian (SAS)

AF:

0.633

AC:

48492

AN:

76638

European-Finnish (FIN)

AF:

0.684

AC:

34007

AN:

49718

Middle Eastern (MID)

AF:

0.529

AC:

2955

AN:

5586

European-Non Finnish (NFE)

AF:

0.634

AC:

676510

AN:

1067436

Other (OTH)

AF:

0.603

AC:

34625

AN:

57408

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

12842

25683

38525

51366

64208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17844

35688

53532

71376

89220

<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:

0.503

AC:

76365

AN:

151934

Hom.:

22244

Cov.:

AF XY:

0.508

AC XY:

37717

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.191

AC:

7919

AN:

41464

American (AMR)

AF:

0.474

AC:

7234

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.635

AC:

2200

AN:

3462

East Asian (EAS)

AF:

0.724

AC:

3742

AN:

5172

South Asian (SAS)

AF:

0.626

AC:

3021

AN:

4828

European-Finnish (FIN)

AF:

0.685

AC:

7224

AN:

10552

Middle Eastern (MID)

AF:

0.541

AC:

157

AN:

290

European-Non Finnish (NFE)

AF:

0.637

AC:

43269

AN:

67886

Other (OTH)

AF:

0.546

AC:

1154

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1654

3309

4963

6618

8272

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

674

1348

2022

2696

3370

<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:

0.602

Hom.:

89318

Bravo

AF:

0.469

TwinsUK

AF:

0.640

AC:

2372

ALSPAC

AF:

0.641

AC:

2470

ESP6500AA

AF:

0.215

AC:

948

ESP6500EA

AF:

0.641

AC:

5509

ExAC

AF:

0.584

AC:

70865

Asia WGS

AF:

0.639

AC:

2207

AN:

3452

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

Asn2237Ser in exon 56 of OTOGL: This variant is not expected to have clinical si gnificance because it has been identified in 35.9% (3089/8598) of European Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs1551122). -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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. -

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

0.15

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.77

T;.;T

MetaRNN

Benign

0.0000046

T;T;T

MetaSVM

Benign

-0.99

PhyloP100

4.5

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-2.4

.;.;N

REVEL

Benign

0.16

Sift

Benign

0.052

.;.;T

Sift4G

Uncertain

0.056

.;.;T

Vest4

0.17

MPC

0.17

ClinPred

0.021

GERP RS

6.0

gMVP

0.39

Mutation Taster

=92/8

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.89

dbscSNV1_RF

Benign

0.30

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over