12-80336781-CTTT-CTT

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001378609.3(OTOGL):c.4744-5delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,133,276 control chromosomes in the GnomAD database, including 22,107 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3084 hom., cov: 26)

Exomes 𝑓: 0.26 ( 19023 hom. )

Consequence

OTOGL
NM_001378609.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.465

Publications

2 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 -16 ACMG points.

BP6

Variant 12-80336781-CT-C is Benign according to our data. Variant chr12-80336781-CT-C is described in ClinVar as Benign. ClinVar VariationId is 226949.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOGL	NM_001378609.3 link	c.4744-5delT		splice_region_variant, intron_variant	Intron 40 of 58	ENST00000547103.7	NP_001365538.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
OTOGL	ENST00000547103.7 link	c.4744-15delT	intron_variant	Intron 40 of 58	5	NM_001378609.3	ENSP00000447211.2	Q3ZCN5
OTOGL	ENST00000646859.1 link	c.4609-15delT	intron_variant	Intron 44 of 62			ENSP00000496036.1	A0A2R8YF04
OTOGL	ENST00000298820.7 link	c.43-15delT	intron_variant	Intron 1 of 17	5		ENSP00000298820.3	H7BXL6

Frequencies

GnomAD3 genomes

AF:

0.202

AC:

29848

AN:

147718

Hom.:

3084

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.288

Gnomad AMR

AF:

0.229

Gnomad ASJ

AF:

0.189

Gnomad EAS

AF:

0.0511

Gnomad SAS

AF:

0.224

Gnomad FIN

AF:

0.120

Gnomad MID

AF:

0.252

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.204

GnomAD2 exomes

AF:

0.361

AC:

26828

AN:

74216

AF XY:

0.366

show subpopulations

Gnomad AFR exome

AF:

0.375

Gnomad AMR exome

AF:

0.385

Gnomad ASJ exome

AF:

0.374

Gnomad EAS exome

AF:

0.177

Gnomad FIN exome

AF:

0.241

Gnomad NFE exome

AF:

0.386

Gnomad OTH exome

AF:

0.387

GnomAD4 exome

AF:

0.265

AC:

260919

AN:

985480

Hom.:

19023

Cov.:

AF XY:

0.267

AC XY:

129569

AN XY:

486034

show subpopulations

African (AFR)

AF:

0.280

AC:

6196

AN:

22110

American (AMR)

AF:

0.282

AC:

7234

AN:

25610

Ashkenazi Jewish (ASJ)

AF:

0.272

AC:

4660

AN:

17146

East Asian (EAS)

AF:

0.0900

AC:

1820

AN:

20212

South Asian (SAS)

AF:

0.295

AC:

16264

AN:

55058

European-Finnish (FIN)

AF:

0.191

AC:

5913

AN:

30942

Middle Eastern (MID)

AF:

0.284

AC:

1055

AN:

3710

European-Non Finnish (NFE)

AF:

0.269

AC:

207032

AN:

770016

Other (OTH)

AF:

0.264

AC:

10745

AN:

40676

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

10445

20890

31336

41781

52226

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7328

14656

21984

29312

36640

<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:

0.202

AC:

29853

AN:

147796

Hom.:

3084

Cov.:

AF XY:

0.199

AC XY:

14304

AN XY:

71988

show subpopulations

African (AFR)

AF:

0.219

AC:

8869

AN:

40572

American (AMR)

AF:

0.229

AC:

3394

AN:

14848

Ashkenazi Jewish (ASJ)

AF:

0.189

AC:

643

AN:

3398

East Asian (EAS)

AF:

0.0512

AC:

258

AN:

5036

South Asian (SAS)

AF:

0.224

AC:

1051

AN:

4686

European-Finnish (FIN)

AF:

0.120

AC:

1142

AN:

9514

Middle Eastern (MID)

AF:

0.250

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.207

AC:

13757

AN:

66544

Other (OTH)

AF:

0.203

AC:

410

AN:

2018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1182

2364

3547

4729

5911

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

314

628

942

1256

1570

<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:

0.0871

Hom.:

104

Bravo

AF:

0.204

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 02, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Nov 05, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

4717-5delT in intron 39 of OTOGL: This variant is not expected to have clinical significance because it has been detected in 5.3% (779/14498) chromosomes across several diverse populations by the Exome Aggregate Consortium (http://exac.broa dinstitute.org/; dbSNP rs11300714). In addition, this variant affects a poly-T t ract in the 3' splice site region, and a deletion of a T at this position does n ot diverge from the splice consensus sequence and is therefore unlikely to impac t splicing. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.47

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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