rs1551118

Positions:

chr12-80367650-G-A

Variant summary

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

The NM_001378609.3(OTOGL):c.6421G>A(p.Ala2141Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 1,525,446 control chromosomes in the GnomAD database, including 503,471 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 40662 hom., cov: 32)

Exomes 𝑓: 0.82 ( 462809 hom. )

Consequence

OTOGL
NM_001378609.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.09

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=9.20896E-7).

BP6

Variant 12-80367650-G-A is Benign according to our data. Variant chr12-80367650-G-A is described in ClinVar as [Benign]. Clinvar id is 226969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-80367650-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTOGL	NM_001378609.3 linkuse as main transcript	c.6421G>A	p.Ala2141Thr	missense_variant	54/59	ENST00000547103.7	NP_001365538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTOGL	ENST00000547103.7 linkuse as main transcript	c.6421G>A	p.Ala2141Thr	missense_variant	54/59	5	NM_001378609.3	ENSP00000447211	P1

Frequencies

GnomAD3 genomes

AF:

0.714

AC:

108418

AN:

151916

Hom.:

40660

Cov.:

show subpopulations

Gnomad AFR

AF:

0.457

Gnomad AMI

AF:

0.774

Gnomad AMR

AF:

0.702

Gnomad ASJ

AF:

0.840

Gnomad EAS

AF:

0.781

Gnomad SAS

AF:

0.813

Gnomad FIN

AF:

0.792

Gnomad MID

AF:

0.782

Gnomad NFE

AF:

0.839

Gnomad OTH

AF:

0.755

GnomAD3 exomes

AF:

0.765

AC:

137747

AN:

180070

Hom.:

53679

AF XY:

0.778

AC XY:

75103

AN XY:

96510

show subpopulations

Gnomad AFR exome

AF:

0.444

Gnomad AMR exome

AF:

0.613

Gnomad ASJ exome

AF:

0.832

Gnomad EAS exome

AF:

0.760

Gnomad SAS exome

AF:

0.816

Gnomad FIN exome

AF:

0.791

Gnomad NFE exome

AF:

0.833

Gnomad OTH exome

AF:

0.777

GnomAD4 exome

AF:

0.818

AC:

1123451

AN:

1373414

Hom.:

462809

Cov.:

AF XY:

0.820

AC XY:

558950

AN XY:

682006

show subpopulations

Gnomad4 AFR exome

AF:

0.436

Gnomad4 AMR exome

AF:

0.633

Gnomad4 ASJ exome

AF:

0.833

Gnomad4 EAS exome

AF:

0.770

Gnomad4 SAS exome

AF:

0.819

Gnomad4 FIN exome

AF:

0.799

Gnomad4 NFE exome

AF:

0.838

Gnomad4 OTH exome

AF:

0.800

GnomAD4 genome

AF:

0.713

AC:

108447

AN:

152032

Hom.:

40662

Cov.:

AF XY:

0.714

AC XY:

53070

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.457

Gnomad4 AMR

AF:

0.702

Gnomad4 ASJ

AF:

0.840

Gnomad4 EAS

AF:

0.780

Gnomad4 SAS

AF:

0.812

Gnomad4 FIN

AF:

0.792

Gnomad4 NFE

AF:

0.839

Gnomad4 OTH

AF:

0.755

Alfa

AF:

0.819

Hom.:

115075

Bravo

AF:

0.691

TwinsUK

AF:

0.833

AC:

3088

ALSPAC

AF:

0.844

AC:

3251

ESP6500AA

AF:

0.483

AC:

2123

ESP6500EA

AF:

0.839

AC:

7198

ExAC

AF:

0.753

AC:

90385

Asia WGS

AF:

0.781

AC:

2708

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 2017	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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	Ala2132Thr in exon 53 of OTOGL: This variant is not expected to have clinical si gnificance because it has been identified in 48.3% (2123/4398) of African Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs1551118). -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

6.0

DANN

Benign

0.20

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.14

T;.;T

MetaRNN

Benign

9.2e-7

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.33

PROVEAN

Benign

2.6

.;.;N

REVEL

Benign

0.031

Sift

Benign

1.0

.;.;T

Sift4G

Benign

1.0

.;.;T

Vest4

0.038

MPC

0.022

ClinPred

0.0014

GERP RS

3.0

gMVP

0.13

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