chr12-80341991-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001378609.3(OTOGL):c.5094T>C(p.Asn1698Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 1,605,588 control chromosomes in the GnomAD database, including 306,149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 22649 hom., cov: 32)

Exomes 𝑓: 0.62 ( 283500 hom. )

Consequence

OTOGL
NM_001378609.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.263

Publications

20 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.032).

BP6

Variant 12-80341991-T-C is Benign according to our data. Variant chr12-80341991-T-C is described in ClinVar as [Benign]. Clinvar id is 226952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.263 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOGL	NM_001378609.3 link	c.5094T>C	p.Asn1698Asn	synonymous_variant	Exon 44 of 59	ENST00000547103.7	NP_001365538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OTOGL	ENST00000547103.7 link	c.5094T>C	p.Asn1698Asn	synonymous_variant	Exon 44 of 59	5	NM_001378609.3	ENSP00000447211.2	Q3ZCN5
OTOGL	ENST00000646859.1 link	c.4959T>C	p.Asn1653Asn	synonymous_variant	Exon 48 of 63			ENSP00000496036.1	A0A2R8YF04
OTOGL	ENST00000298820.7 link	c.393T>C	p.Asn131Asn	synonymous_variant	Exon 5 of 18	5		ENSP00000298820.3	H7BXL6

Frequencies

GnomAD3 genomes

AF:

0.519

AC:

78823

AN:

151906

Hom.:

22649

Cov.:

show subpopulations

Gnomad AFR

AF:

0.256

Gnomad AMI

AF:

0.488

Gnomad AMR

AF:

0.479

Gnomad ASJ

AF:

0.629

Gnomad EAS

AF:

0.719

Gnomad SAS

AF:

0.596

Gnomad FIN

AF:

0.683

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.635

Gnomad OTH

AF:

0.554

GnomAD2 exomes

AF:

0.584

AC:

139845

AN:

239328

AF XY:

0.596

show subpopulations

Gnomad AFR exome

AF:

0.246

Gnomad AMR exome

AF:

0.405

Gnomad ASJ exome

AF:

0.625

Gnomad EAS exome

AF:

0.709

Gnomad FIN exome

AF:

0.687

Gnomad NFE exome

AF:

0.637

Gnomad OTH exome

AF:

0.590

GnomAD4 exome

AF:

0.620

AC:

900538

AN:

1453564

Hom.:

283500

Cov.:

AF XY:

0.621

AC XY:

448778

AN XY:

722732

show subpopulations

African (AFR)

AF:

0.240

AC:

8004

AN:

33394

American (AMR)

AF:

0.415

AC:

18325

AN:

44120

Ashkenazi Jewish (ASJ)

AF:

0.620

AC:

16129

AN:

26004

East Asian (EAS)

AF:

0.726

AC:

28717

AN:

39534

South Asian (SAS)

AF:

0.608

AC:

51692

AN:

85024

European-Finnish (FIN)

AF:

0.687

AC:

36531

AN:

53204

Middle Eastern (MID)

AF:

0.529

AC:

3028

AN:

5720

European-Non Finnish (NFE)

AF:

0.634

AC:

701683

AN:

1106422

Other (OTH)

AF:

0.606

AC:

36429

AN:

60142

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

15504

31008

46511

62015

77519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.519

AC:

78837

AN:

152024

Hom.:

22649

Cov.:

AF XY:

0.523

AC XY:

38829

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.256

AC:

10620

AN:

41494

American (AMR)

AF:

0.479

AC:

7318

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.629

AC:

2183

AN:

3472

East Asian (EAS)

AF:

0.718

AC:

3707

AN:

5162

South Asian (SAS)

AF:

0.596

AC:

2873

AN:

4824

European-Finnish (FIN)

AF:

0.683

AC:

7216

AN:

10560

Middle Eastern (MID)

AF:

0.548

AC:

160

AN:

292

European-Non Finnish (NFE)

AF:

0.635

AC:

43145

AN:

67936

Other (OTH)

AF:

0.555

AC:

1170

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1721

3443

5164

6886

8607

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.588

Hom.:

81076

Bravo

AF:

0.488

Asia WGS

AF:

0.631

AC:

2192

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

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. -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Asn1689Asn in exon 43 of OTOGL: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 36.2% (2963/8184) of European American chromosomes from a broad population by the NHLBI Exome Sequ encing Project (http://evs.gs.washington.edu/EVS; dbSNP rs10778727). -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

6.1

(source)

DANN

Benign

0.80

PhyloP100

0.26

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

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chr12-80341991-T-C

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