rs875696

Variant names:

• chr11-17593702-C-A
• rs875696
• NM_001292063.2:c.3234C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-17593702-C-A
• chr11-17593702-C-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001292063.2(OTOG):​c.3234C>A​(p.Thr1078Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0401 in 1,548,812 control chromosomes in the GnomAD database, including 1,570 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (306 hom., cov: 32)
  • Exomes 𝑓: 0.039 (1264 hom.)
• Consequence: OTOG NM_001292063.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.660
• 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 11-17593702-C-A is Benign according to our data. Variant chr11-17593702-C-A is described in ClinVar as Benign. ClinVar VariationId is 226880.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.66 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0966 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001292063.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOG	NM_001292063.2	MANE Select	c.3234C>A	p.Thr1078Thr	synonymous	Exon 27 of 56	NP_001278992.1
	OTOG	NM_001277269.2		c.3270C>A	p.Thr1090Thr	synonymous	Exon 26 of 55	NP_001264198.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOG	ENST00000399397.6	TSL:5 MANE Select	c.3234C>A	p.Thr1078Thr	synonymous	Exon 27 of 56	ENSP00000382329.2
	OTOG	ENST00000399391.7	TSL:5	c.3270C>A	p.Thr1090Thr	synonymous	Exon 26 of 55	ENSP00000382323.2
	OTOG	ENST00000342528.2	TSL:2	n.599C>A		non_coding_transcript_exon	Exon 4 of 22

Frequencies

GnomAD3 genomes AF: 0.0538 AC: 8181 AN: 152094 Hom.: 304 Cov.: 32

Gnomad AFR AF: 0.0989

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0580

Gnomad ASJ AF: 0.0210

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0754

Gnomad FIN AF: 0.0341

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0337

Gnomad OTH AF: 0.0355

GnomAD2 exomes AF: 0.0422 AC: 6258 AN: 148464 AF XY: 0.0432

Gnomad AFR exome AF: 0.0983

Gnomad AMR exome AF: 0.0471

Gnomad ASJ exome AF: 0.0255

Gnomad EAS exome AF: 0.000556

Gnomad FIN exome AF: 0.0326

Gnomad NFE exome AF: 0.0319

Gnomad OTH exome AF: 0.0346

GnomAD4 exome AF: 0.0386 AC: 53946 AN: 1396600 Hom.: 1264 Cov.: 32 AF XY: 0.0395 AC XY: 27220 AN XY: 688840

African (AFR) AF: 0.0989 AC: 3119 AN: 31538

American (AMR) AF: 0.0459 AC: 1640 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.0253 AC: 637 AN: 25182

East Asian (EAS) AF: 0.000783 AC: 28 AN: 35738

South Asian (SAS) AF: 0.0788 AC: 6235 AN: 79158

European-Finnish (FIN) AF: 0.0313 AC: 1507 AN: 48166

Middle Eastern (MID) AF: 0.0164 AC: 71 AN: 4342

European-Non Finnish (NFE) AF: 0.0358 AC: 38611 AN: 1078926

Other (OTH) AF: 0.0363 AC: 2098 AN: 57848

GnomAD4 genome AF: 0.0539 AC: 8208 AN: 152212 Hom.: 306 Cov.: 32 AF XY: 0.0553 AC XY: 4117 AN XY: 74422

African (AFR) AF: 0.0991 AC: 4117 AN: 41534

American (AMR) AF: 0.0581 AC: 889 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0210 AC: 73 AN: 3472

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5180

South Asian (SAS) AF: 0.0759 AC: 365 AN: 4812

European-Finnish (FIN) AF: 0.0341 AC: 362 AN: 10608

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0337 AC: 2290 AN: 67998

Other (OTH) AF: 0.0351 AC: 74 AN: 2108

Alfa AF: 0.0380 Hom.: 218

Bravo AF: 0.0542

Asia WGS AF: 0.0510 AC: 178 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	9.4
DANN	Benign	0.59
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs875696; hg19: chr11-17615249;