12-80302695-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001378609.3(OTOGL):c.3125A>G(p.Tyr1042Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00554 in 1,515,082 control chromosomes in the GnomAD database, including 392 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 217 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 175 hom. )

Consequence

OTOGL
NM_001378609.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 8.43

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036207438).

BP6

Variant 12-80302695-A-G is Benign according to our data. Variant chr12-80302695-A-G is described in ClinVar as [Benign]. Clinvar id is 226937.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-80302695-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOGL	NM_001378609.3 link	c.3125A>G	p.Tyr1042Cys	missense_variant	Exon 28 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.3125A>G	p.Tyr1042Cys	missense_variant	Exon 28 of 59	5	NM_001378609.3	ENSP00000447211.2		Q3ZCN5
OTOGL	ENST00000646859.1 link	c.2990A>G	p.Tyr997Cys	missense_variant	Exon 32 of 63			ENSP00000496036.1		A0A2R8YF04

Frequencies

GnomAD3 genomes

AF:

0.0287

AC:

4372

AN:

152184

Hom.:

217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.100

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0100

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.0196

GnomAD3 exomes

AF:

0.00716

AC:

1124

AN:

156942

Hom.:

AF XY:

0.00515

AC XY:

438

AN XY:

84978

show subpopulations

Gnomad AFR exome

AF:

0.0953

Gnomad AMR exome

AF:

0.00567

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000321

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000297

Gnomad OTH exome

AF:

0.00401

GnomAD4 exome

AF:

0.00295

AC:

4016

AN:

1362780

Hom.:

175

Cov.:

AF XY:

0.00255

AC XY:

1716

AN XY:

673262

show subpopulations

Gnomad4 AFR exome

AF:

0.103

Gnomad4 AMR exome

AF:

0.00578

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000324

Gnomad4 SAS exome

AF:

0.0000968

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000190

Gnomad4 OTH exome

AF:

0.00712

GnomAD4 genome

AF:

0.0288

AC:

4385

AN:

152302

Hom.:

217

Cov.:

AF XY:

0.0277

AC XY:

2062

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.100

Gnomad4 AMR

AF:

0.0100

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.00136

Hom.:

Bravo

AF:

0.0324

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0951

AC:

343

ESP6500EA

AF:

0.000246

AC:

ExAC

AF:

0.00762

AC:

898

Asia WGS

AF:

0.00405

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Oct 23, 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

Tyr1033Cys in exon 27 of OTOGL: This variant is not expected to have clinical si gnificance because it has been identified in 9.5% (343/3608) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs12304169). -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 30, 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

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.92

D;.;D

MetaRNN

Benign

0.0036

T;T;T

MetaSVM

Benign

-0.86

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-6.8

.;.;D

REVEL

Uncertain

0.57

Sift

Uncertain

0.0010

.;.;D

Sift4G

Pathogenic

0.0010

.;.;D

Vest4

0.83

MVP

0.51

MPC

0.18

ClinPred

0.035

GERP RS

5.7

gMVP

0.96

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over