NM_001378609.3:c.5060A>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.5060A>G(p.Asn1687Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0483 in 1,600,182 control chromosomes in the GnomAD database, including 2,220 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 158 hom., cov: 32)

Exomes 𝑓: 0.050 ( 2062 hom. )

Consequence

OTOGL
NM_001378609.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 7.16

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=0.0050604045).

BP6

Variant 12-80341957-A-G is Benign according to our data. Variant chr12-80341957-A-G is described in ClinVar as [Benign]. Clinvar id is 226950.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-80341957-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOGL	NM_001378609.3 link	c.5060A>G	p.Asn1687Ser	missense_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.5060A>G	p.Asn1687Ser	missense_variant	Exon 44 of 59	5	NM_001378609.3	ENSP00000447211.2	Q3ZCN5
OTOGL	ENST00000646859.1 link	c.4925A>G	p.Asn1642Ser	missense_variant	Exon 48 of 63			ENSP00000496036.1	A0A2R8YF04
OTOGL	ENST00000298820.7 link	c.359A>G	p.Asn120Ser	missense_variant	Exon 5 of 18	5		ENSP00000298820.3	H7BXL6

Frequencies

GnomAD3 genomes

AF:

0.0360

AC:

5482

AN:

152164

Hom.:

159

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00997

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.0549

Gnomad ASJ

AF:

0.0467

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.0162

Gnomad FIN

AF:

0.0129

Gnomad MID

AF:

0.0605

Gnomad NFE

AF:

0.0541

Gnomad OTH

AF:

0.0488

GnomAD3 exomes

AF:

0.0370

AC:

8624

AN:

233194

Hom.:

220

AF XY:

0.0373

AC XY:

4701

AN XY:

125920

show subpopulations

Gnomad AFR exome

AF:

0.00880

Gnomad AMR exome

AF:

0.0378

Gnomad ASJ exome

AF:

0.0488

Gnomad EAS exome

AF:

0.000116

Gnomad SAS exome

AF:

0.0185

Gnomad FIN exome

AF:

0.0155

Gnomad NFE exome

AF:

0.0545

Gnomad OTH exome

AF:

0.0498

GnomAD4 exome

AF:

0.0496

AC:

71810

AN:

1447900

Hom.:

2062

Cov.:

AF XY:

0.0489

AC XY:

35170

AN XY:

719514

show subpopulations

Gnomad4 AFR exome

AF:

0.00895

Gnomad4 AMR exome

AF:

0.0389

Gnomad4 ASJ exome

AF:

0.0477

Gnomad4 EAS exome

AF:

0.000152

Gnomad4 SAS exome

AF:

0.0180

Gnomad4 FIN exome

AF:

0.0156

Gnomad4 NFE exome

AF:

0.0571

Gnomad4 OTH exome

AF:

0.0471

GnomAD4 genome

AF:

0.0360

AC:

5479

AN:

152282

Hom.:

158

Cov.:

AF XY:

0.0348

AC XY:

2592

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00994

Gnomad4 AMR

AF:

0.0548

Gnomad4 ASJ

AF:

0.0467

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0160

Gnomad4 FIN

AF:

0.0129

Gnomad4 NFE

AF:

0.0541

Gnomad4 OTH

AF:

0.0483

Alfa

AF:

0.0517

Hom.:

350

Bravo

AF:

0.0384

TwinsUK

AF:

0.0580

AC:

215

ALSPAC

AF:

0.0563

AC:

217

ESP6500AA

AF:

0.0114

AC:

ESP6500EA

AF:

0.0552

AC:

451

ExAC

AF:

0.0362

AC:

4366

Asia WGS

AF:

0.00983

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

Aug 25, 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

Asn1678Ser in exon 43 of OTOGL: This variant is not expected to have clinical si gnificance because it has been identified in 5.5% (451/8174) of European America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs61735664). -

not provided

Benign:2

Jan 29, 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_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.41

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

D;.;D

MetaRNN

Benign

0.0051

T;T;T

MetaSVM

Benign

-0.58

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.2

.;.;D

REVEL

Benign

0.24

Sift

Uncertain

0.012

.;.;D

Sift4G

Uncertain

0.015

.;.;D

Vest4

0.51

MPC

0.17

ClinPred

0.0041

GERP RS

5.0

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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