rs10778725

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001378609.3(OTOGL):c.3729G>A(p.Pro1243Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.974 in 1,468,996 control chromosomes in the GnomAD database, including 697,666 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.96 ( 70633 hom., cov: 31)

Exomes 𝑓: 0.98 ( 627033 hom. )

Consequence

OTOGL
NM_001378609.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.525

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 12-80318640-G-A is Benign according to our data. Variant chr12-80318640-G-A is described in ClinVar as [Benign]. Clinvar id is 226944.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-80318640-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.525 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOGL	NM_001378609.3 link	c.3729G>A	p.Pro1243Pro	synonymous_variant	Exon 33 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.3729G>A	p.Pro1243Pro	synonymous_variant	Exon 33 of 59	5	NM_001378609.3	ENSP00000447211.2		Q3ZCN5
OTOGL	ENST00000646859.1 link	c.3594G>A	p.Pro1198Pro	synonymous_variant	Exon 37 of 63			ENSP00000496036.1		A0A2R8YF04

Frequencies

GnomAD3 genomes

AF:

0.963

AC:

146431

AN:

152102

Hom.:

70575

Cov.:

show subpopulations

Gnomad AFR

AF:

0.955

Gnomad AMI

AF:

0.980

Gnomad AMR

AF:

0.898

Gnomad ASJ

AF:

0.974

Gnomad EAS

AF:

0.948

Gnomad SAS

AF:

0.938

Gnomad FIN

AF:

0.972

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

0.982

Gnomad OTH

AF:

0.972

GnomAD3 exomes

AF:

0.949

AC:

99078

AN:

104450

Hom.:

47231

AF XY:

0.952

AC XY:

53608

AN XY:

56340

show subpopulations

Gnomad AFR exome

AF:

0.945

Gnomad AMR exome

AF:

0.817

Gnomad ASJ exome

AF:

0.973

Gnomad EAS exome

AF:

0.934

Gnomad SAS exome

AF:

0.941

Gnomad FIN exome

AF:

0.971

Gnomad NFE exome

AF:

0.981

Gnomad OTH exome

AF:

0.960

GnomAD4 exome

AF:

0.976

AC:

1284595

AN:

1316776

Hom.:

627033

Cov.:

AF XY:

0.975

AC XY:

631963

AN XY:

648196

show subpopulations

Gnomad4 AFR exome

AF:

0.954

Gnomad4 AMR exome

AF:

0.844

Gnomad4 ASJ exome

AF:

0.972

Gnomad4 EAS exome

AF:

0.954

Gnomad4 SAS exome

AF:

0.944

Gnomad4 FIN exome

AF:

0.972

Gnomad4 NFE exome

AF:

0.982

Gnomad4 OTH exome

AF:

0.973

GnomAD4 genome

AF:

0.963

AC:

146548

AN:

152220

Hom.:

70633

Cov.:

AF XY:

0.961

AC XY:

71483

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.955

Gnomad4 AMR

AF:

0.898

Gnomad4 ASJ

AF:

0.974

Gnomad4 EAS

AF:

0.949

Gnomad4 SAS

AF:

0.938

Gnomad4 FIN

AF:

0.972

Gnomad4 NFE

AF:

0.982

Gnomad4 OTH

AF:

0.973

Alfa

AF:

0.970

Hom.:

43721

Bravo

AF:

0.956

Asia WGS

AF:

0.943

AC:

3274

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

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. -

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Pro1234Pro in exon 32 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 4.5% (160/3556) of African American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs10778725). -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 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_noAF

Benign

-0.70

CADD

Benign

5.5

DANN

Benign

0.51

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