rs143393149

Positions:

chr11-17596943-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001292063.2(OTOG):c.3618C>T(p.Ser1206=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,550,718 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 26 hom. )

Consequence

OTOG
NM_001292063.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.19

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 11-17596943-C-T is Benign according to our data. Variant chr11-17596943-C-T is described in ClinVar as [Benign]. Clinvar id is 226889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.19 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00243 (370/152294) while in subpopulation EAS AF= 0.0512 (265/5178). AF 95% confidence interval is 0.0461. There are 6 homozygotes in gnomad4. There are 207 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTOG	NM_001292063.2 linkuse as main transcript	c.3618C>T	p.Ser1206=	synonymous_variant	30/56	ENST00000399397.6	NP_001278992.1
OTOG	NM_001277269.2 linkuse as main transcript	c.3654C>T	p.Ser1218=	synonymous_variant	29/55		NP_001264198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTOG	ENST00000399397.6 linkuse as main transcript	c.3618C>T	p.Ser1206=	synonymous_variant	30/56	5	NM_001292063.2	ENSP00000382329	P2
OTOG	ENST00000399391.7 linkuse as main transcript	c.3654C>T	p.Ser1218=	synonymous_variant	29/55	5		ENSP00000382323	A2	Q6ZRI0-1
OTOG	ENST00000342528.2 linkuse as main transcript	n.983C>T		non_coding_transcript_exon_variant	7/22	2

Frequencies

GnomAD3 genomes

AF:

0.00244

AC:

372

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0514

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00458

AC:

685

AN:

149724

Hom.:

AF XY:

0.00449

AC XY:

362

AN XY:

80554

show subpopulations

Gnomad AFR exome

AF:

0.00132

Gnomad AMR exome

AF:

0.000285

Gnomad ASJ exome

AF:

0.000119

Gnomad EAS exome

AF:

0.0558

Gnomad SAS exome

AF:

0.00173

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000541

Gnomad OTH exome

AF:

0.00552

GnomAD4 exome

AF:

0.00128

AC:

1791

AN:

1398424

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

868

AN XY:

689736

show subpopulations

Gnomad4 AFR exome

AF:

0.000601

Gnomad4 AMR exome

AF:

0.000252

Gnomad4 ASJ exome

AF:

0.0000794

Gnomad4 EAS exome

AF:

0.0350

Gnomad4 SAS exome

AF:

0.00170

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000639

Gnomad4 OTH exome

AF:

0.00527

GnomAD4 genome

AF:

0.00243

AC:

370

AN:

152294

Hom.:

Cov.:

AF XY:

0.00278

AC XY:

207

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0512

Gnomad4 SAS

AF:

0.00395

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000556

Hom.:

Bravo

AF:

0.00250

Asia WGS

AF:

0.0340

AC:

117

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 31, 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	Ser1218Ser in exon 29 of OTOG: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 3.5% (7/200) of Han Chinese chromosomes from a broad population by the 1000 Genomes Project (http:/ /www.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs143393149). -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Oct 28, 2019	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 18, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

2.2

DANN

Benign

0.77

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