11-17552020-C-T

Variant names:

• chr11-17552020-C-T
• rs11823045
• NM_001292063.2:c.237C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001292063.2(OTOG):​c.237C>T​(p.Ser79Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0293 in 1,550,372 control chromosomes in the GnomAD database, including 3,658 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.093 (1866 hom., cov: 33)
  • Exomes 𝑓: 0.022 (1792 hom.)
• Consequence: OTOG NM_001292063.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.355
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 18B

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Laboratory for Molecular Medicine, Ambry Genetics
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 11-17552020-C-T is Benign according to our data. Variant chr11-17552020-C-T is described in ClinVar as Benign. ClinVar VariationId is 226872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.355 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOG	NM_001292063.2	c.237C>T	p.Ser79Ser	synonymous_variant	Exon 4 of 56	ENST00000399397.6	NP_001278992.1
OTOG	NM_001277269.2	c.273C>T	p.Ser91Ser	synonymous_variant	Exon 3 of 55		NP_001264198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTOG	ENST00000399397.6	c.237C>T	p.Ser79Ser	synonymous_variant	Exon 4 of 56	5	NM_001292063.2	ENSP00000382329.2
OTOG	ENST00000399391.7	c.273C>T	p.Ser91Ser	synonymous_variant	Exon 3 of 55	5		ENSP00000382323.2
OTOG	ENST00000428619.1	c.54C>T	p.Ser18Ser	synonymous_variant	Exon 2 of 4	3		ENSP00000399057.2
OTOG	ENST00000498332.5	n.143C>T		non_coding_transcript_exon_variant	Exon 3 of 16	5

Frequencies

GnomAD3 genomes AF: 0.0927 AC: 14104 AN: 152086 Hom.: 1858 Cov.: 33

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0389

Gnomad ASJ AF: 0.0528

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0159

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0149

Gnomad OTH AF: 0.0722

GnomAD2 exomes AF: 0.0293 AC: 4370 AN: 149212 AF XY: 0.0266

Gnomad AFR exome AF: 0.306

Gnomad AMR exome AF: 0.0193

Gnomad ASJ exome AF: 0.0494

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00553

Gnomad NFE exome AF: 0.0159

Gnomad OTH exome AF: 0.0317

GnomAD4 exome AF: 0.0224 AC: 31308 AN: 1398168 Hom.: 1792 Cov.: 31 AF XY: 0.0215 AC XY: 14818 AN XY: 689634

African (AFR) AF: 0.305 AC: 9620 AN: 31582

American (AMR) AF: 0.0226 AC: 805 AN: 35692

Ashkenazi Jewish (ASJ) AF: 0.0492 AC: 1239 AN: 25176

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35738

South Asian (SAS) AF: 0.0135 AC: 1068 AN: 79230

European-Finnish (FIN) AF: 0.00525 AC: 253 AN: 48192

Middle Eastern (MID) AF: 0.0569 AC: 324 AN: 5698

European-Non Finnish (NFE) AF: 0.0147 AC: 15841 AN: 1078874

Other (OTH) AF: 0.0372 AC: 2157 AN: 57986

GnomAD4 genome AF: 0.0929 AC: 14147 AN: 152204 Hom.: 1866 Cov.: 33 AF XY: 0.0898 AC XY: 6681 AN XY: 74414

African (AFR) AF: 0.291 AC: 12075 AN: 41486

American (AMR) AF: 0.0388 AC: 593 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0528 AC: 183 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.0162 AC: 78 AN: 4826

European-Finnish (FIN) AF: 0.00339 AC: 36 AN: 10624

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0149 AC: 1014 AN: 68004

Other (OTH) AF: 0.0715 AC: 151 AN: 2112

Alfa AF: 0.0447 Hom.: 454

Bravo AF: 0.105

Asia WGS AF: 0.0290 AC: 100 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 23, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:2

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Ser91Ser in exon 3 of OTOG: This variant is not expected to have clinical signif icance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 45.4% (88/194) of Luhy a (Kenyan) chromosomes from a broad population by the 1000 Genomes Project (http ://www.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs11823045). -

Oct 05, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.5
DANN	Benign	0.56
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11823045; hg19: chr11-17573567;