rs542151771

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7

The NM_001292063.2(OTOG):c.8646G>A(p.Leu2882=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000809 in 1,550,798 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00056 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00084 ( 4 hom. )

Consequence

OTOG
NM_001292063.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.35

Variant links:

Genes affected

OTOG (HGNC:8516): (otogelin) The protein encoded by this gene is a component of the acellular membranes of the inner ear. Disruption of the orthologous mouse gene shows that it plays a role in auditory and vestibular functions. It is involved in fibrillar network organization, the anchoring of otoconial membranes and cupulae to the neuroepithelia, and likely in sound stimulation resistance. Mutations in this gene cause autosomal recessive nonsyndromic deafness, type 18B. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2014]

OTOG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 11-17645848-G-A is Benign according to our data. Variant chr11-17645848-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 227808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.35 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTOG	NM_001292063.2 linkuse as main transcript	c.8646G>A	p.Leu2882=	synonymous_variant	56/56	ENST00000399397.6
OTOG	NM_001277269.2 linkuse as main transcript	c.8682G>A	p.Leu2894=	synonymous_variant	55/55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTOG	ENST00000399397.6 linkuse as main transcript	c.8646G>A	p.Leu2882=	synonymous_variant	56/56	5	NM_001292063.2	P2
OTOG	ENST00000399391.7 linkuse as main transcript	c.8682G>A	p.Leu2894=	synonymous_variant	55/55	5		A2	Q6ZRI0-1

Frequencies

GnomAD3 genomes

AF:

0.000565

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000911

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000965

AC:

145

AN:

150224

Hom.:

AF XY:

0.000743

AC XY:

AN XY:

80722

show subpopulations

Gnomad AFR exome

AF:

0.000145

Gnomad AMR exome

AF:

0.00236

Gnomad ASJ exome

AF:

0.000238

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000591

Gnomad NFE exome

AF:

0.00118

Gnomad OTH exome

AF:

0.00389

GnomAD4 exome

AF:

0.000836

AC:

1169

AN:

1398552

Hom.:

Cov.:

AF XY:

0.000784

AC XY:

541

AN XY:

689800

show subpopulations

Gnomad4 AFR exome

AF:

0.000222

Gnomad4 AMR exome

AF:

0.00272

Gnomad4 ASJ exome

AF:

0.000199

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000505

Gnomad4 FIN exome

AF:

0.000145

Gnomad4 NFE exome

AF:

0.000912

Gnomad4 OTH exome

AF:

0.000896

GnomAD4 genome

AF:

0.000565

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000911

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000900

Hom.:

Bravo

AF:

0.000688

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2023	OTOG: BP4 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 24, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 12, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 17, 2019	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jan 14, 2016

p.Leu2894Leu in exon 55 of OTOG: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 5/5654 European c hromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute .org; dbSNP rs542151771). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

Cadd

Benign

8.9

Dann

Benign

0.79

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