11-17593282-C-T

Position:

• chr11-17593282-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001292063.2(OTOG):​c.3096C>T​(p.Asn1032=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,550,482 control chromosomes in the GnomAD database, including 142 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0093 (7 hom., cov: 33)
  • Exomes 𝑓: 0.013 (135 hom.)
• Consequence: OTOG NM_001292063.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.85

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]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 11-17593282-C-T is Benign according to our data. Variant chr11-17593282-C-T is described in ClinVar as [Benign]. Clinvar id is 226878.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.85 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00927 (1412/152308) while in subpopulation NFE AF= 0.0153 (1043/68026). AF 95% confidence interval is 0.0146. There are 7 homozygotes in gnomad4. There are 662 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTOG	NM_001292063.2	c.3096C>T	p.Asn1032=	synonymous_variant	26/56	ENST00000399397.6	NP_001278992.1
OTOG	NM_001277269.2	c.3132C>T	p.Asn1044=	synonymous_variant	25/55		NP_001264198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTOG	ENST00000399397.6	c.3096C>T	p.Asn1032=	synonymous_variant	26/56	5	NM_001292063.2	ENSP00000382329	P2
OTOG	ENST00000399391.7	c.3132C>T	p.Asn1044=	synonymous_variant	25/55	5		ENSP00000382323	A2
OTOG	ENST00000342528.2	n.461C>T		non_coding_transcript_exon_variant	3/22	2

Frequencies

GnomAD3 genomes AF: 0.00928 AC: 1412 AN: 152190 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.00273

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00844

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00580

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0153

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.00978 AC: 1459 AN: 149248 Hom.: 12 AF XY: 0.0102 AC XY: 823 AN XY: 80384

Gnomad AFR exome AF: 0.00133

Gnomad AMR exome AF: 0.00635

Gnomad ASJ exome AF: 0.0201

Gnomad EAS exome AF: 0.0000927

Gnomad SAS exome AF: 0.00657

Gnomad FIN exome AF: 0.00291

Gnomad NFE exome AF: 0.0159

Gnomad OTH exome AF: 0.0116

GnomAD4 exome AF: 0.0127 AC: 17807 AN: 1398174 Hom.: 135 Cov.: 31 AF XY: 0.0127 AC XY: 8728 AN XY: 689618

Gnomad4 AFR exome AF: 0.00215

Gnomad4 AMR exome AF: 0.00770

Gnomad4 ASJ exome AF: 0.0197

Gnomad4 EAS exome AF: 0.0000560

Gnomad4 SAS exome AF: 0.00641

Gnomad4 FIN exome AF: 0.00309

Gnomad4 NFE exome AF: 0.0143

Gnomad4 OTH exome AF: 0.0129

GnomAD4 genome AF: 0.00927 AC: 1412 AN: 152308 Hom.: 7 Cov.: 33 AF XY: 0.00889 AC XY: 662 AN XY: 74484

Gnomad4 AFR AF: 0.00272

Gnomad4 AMR AF: 0.00837

Gnomad4 ASJ AF: 0.0156

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00622

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.0153

Gnomad4 OTH AF: 0.0113

Alfa AF: 0.0135 Hom.: 7

Bravo AF: 0.0100

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 16, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 04, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Nov 24, 2014

Asn1044Asn in exon 25 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 4.5% (5/110) of Pue rto Rican chromosomes from a broad population by the 1000 Genomes Project (http: //www.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs75133799). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	0.45
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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

Other links and lift over

dbSNP: rs75133799; hg19: chr11-17614829; COSMIC: COSV61127745;