11-17634959-C-G

Variant names:

• chr11-17634959-C-G
• rs369343034
• NM_001292063.2:c.7585+11C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001292063.2(OTOG):​c.7585+11C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000082 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00057 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OTOG NM_001292063.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOG	NM_001292063.2	c.7585+11C>G		intron_variant	Intron 45 of 55	ENST00000399397.6	NP_001278992.1
OTOG	NM_001277269.2	c.7621+11C>G		intron_variant	Intron 44 of 54		NP_001264198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTOG	ENST00000399397.6	c.7585+11C>G		intron_variant	Intron 45 of 55	5	NM_001292063.2	ENSP00000382329.2
OTOG	ENST00000399391.7	c.7621+11C>G		intron_variant	Intron 44 of 54	5		ENSP00000382323.2
OTOG	ENST00000342528.2	n.4606-651C>G		intron_variant	Intron 19 of 21	2

Frequencies

GnomAD3 genomes AF: 0.0000824 AC: 8 AN: 97112 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.000113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000364

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000184 AC: 22 AN: 119620 AF XY: 0.000167

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000120

Gnomad ASJ exome AF: 0.000316

Gnomad EAS exome AF: 0.000112

Gnomad FIN exome AF: 0.000439

Gnomad NFE exome AF: 0.000154

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000573 AC: 220 AN: 384236 Hom.: 0 Cov.: 0 AF XY: 0.000508 AC XY: 105 AN XY: 206828

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000784 AC: 9 AN: 11486

American (AMR) AF: 0.00214 AC: 42 AN: 19616

Ashkenazi Jewish (ASJ) AF: 0.000397 AC: 4 AN: 10064

East Asian (EAS) AF: 0.00 AC: 0 AN: 10514

South Asian (SAS) AF: 0.000417 AC: 22 AN: 52810

European-Finnish (FIN) AF: 0.000123 AC: 3 AN: 24484

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2176

European-Non Finnish (NFE) AF: 0.000558 AC: 132 AN: 236510

Other (OTH) AF: 0.000483 AC: 8 AN: 16576

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000824 AC: 8 AN: 97140 Hom.: 0 Cov.: 28 AF XY: 0.000105 AC XY: 5 AN XY: 47416

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000113 AC: 3 AN: 26622

American (AMR) AF: 0.00 AC: 0 AN: 9886

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2510

East Asian (EAS) AF: 0.00 AC: 0 AN: 3152

South Asian (SAS) AF: 0.000365 AC: 1 AN: 2742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4764

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 188

European-Non Finnish (NFE) AF: 0.0000881 AC: 4 AN: 45378

Other (OTH) AF: 0.00 AC: 0 AN: 1336

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000115187), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000565 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.55
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs369343034; hg19: chr11-17656506;