Variant 11-17645640-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_Very_StrongBP7BS2_Supporting

The NM_001292063.2(OTOG):c.8538C>T(p.Thr2846=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000681 in 1,550,710 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00069 ( 2 hom. )

Consequence

OTOG
NM_001292063.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.133

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 11-17645640-C-T is Benign according to our data. Variant chr11-17645640-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 735307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17645640-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.133 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTOG	NM_001292063.2 linkuse as main transcript	c.8538C>T	p.Thr2846=	synonymous_variant	55/56	ENST00000399397.6	NP_001278992.1
OTOG	NM_001277269.2 linkuse as main transcript	c.8574C>T	p.Thr2858=	synonymous_variant	54/55		NP_001264198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTOG	ENST00000399397.6 linkuse as main transcript	c.8538C>T	p.Thr2846=	synonymous_variant	55/56	5	NM_001292063.2	ENSP00000382329	P2
OTOG	ENST00000399391.7 linkuse as main transcript	c.8574C>T	p.Thr2858=	synonymous_variant	54/55	5		ENSP00000382323	A2	Q6ZRI0-1

Frequencies

GnomAD3 genomes

AF:

0.000604

AC:

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000981

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00103

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000456

AC:

AN:

149238

Hom.:

AF XY:

0.000361

AC XY:

AN XY:

80374

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000895

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000119

Gnomad NFE exome

AF:

0.000763

Gnomad OTH exome

AF:

0.000463

GnomAD4 exome

AF:

0.000689

AC:

964

AN:

1398328

Hom.:

Cov.:

AF XY:

0.000700

AC XY:

483

AN XY:

689692

show subpopulations

Gnomad4 AFR exome

AF:

0.0000633

Gnomad4 AMR exome

AF:

0.000756

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000166

Gnomad4 NFE exome

AF:

0.000829

Gnomad4 OTH exome

AF:

0.000569

GnomAD4 genome

AF:

0.000604

AC:

AN:

152382

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74522

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00103

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000869

Hom.:

Bravo

AF:

0.000642

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 11, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 25, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

0.92

DANN

Benign

0.62

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