Variant 11-17561786-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7

The NM_001292063.2(OTOG):c.1623G>A(p.Leu541=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000632 in 1,550,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

OTOG
NM_001292063.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.660

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 -9 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 11-17561786-G-A is Benign according to our data. Variant chr11-17561786-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 505680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.66 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTOG	NM_001292063.2 linkuse as main transcript	c.1623G>A	p.Leu541=	synonymous_variant	15/56	ENST00000399397.6	NP_001278992.1
OTOG	NM_001277269.2 linkuse as main transcript	c.1659G>A	p.Leu553=	synonymous_variant	14/55		NP_001264198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTOG	ENST00000399397.6 linkuse as main transcript	c.1623G>A	p.Leu541=	synonymous_variant	15/56	5	NM_001292063.2	ENSP00000382329	P2
OTOG	ENST00000399391.7 linkuse as main transcript	c.1659G>A	p.Leu553=	synonymous_variant	14/55	5		ENSP00000382323	A2	Q6ZRI0-1
OTOG	ENST00000498332.5 linkuse as main transcript	n.1529G>A		non_coding_transcript_exon_variant	14/16	5

Frequencies

GnomAD3 genomes

AF:

0.000335

AC:

AN:

152028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000738

AC:

AN:

149092

Hom.:

AF XY:

0.0000623

AC XY:

AN XY:

80308

show subpopulations

Gnomad AFR exome

AF:

0.00163

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000336

AC:

AN:

1398240

Hom.:

Cov.:

AF XY:

0.0000276

AC XY:

AN XY:

689652

show subpopulations

Gnomad4 AFR exome

AF:

0.00142

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000345

GnomAD4 genome

AF:

0.000335

AC:

AN:

152028

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000305

Hom.:

Bravo

AF:

0.000404

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 31, 2017

p.Leu553Leu in exon 14 of OTOG: 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 0.3% (3/910) of Af rican chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadin stitute.org; dbSNP rs755383141). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 20, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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