rs183555119

Variant names:

• chr12-80352336-T-C
• rs183555119
• NM_001378609.3:c.5307T>C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_Strong BP7 BS1 BS2

The NM_001378609.3(OTOGL):​c.5307T>C​(p.Tyr1769Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00275 in 1,612,054 control chromosomes in the GnomAD database, including 14 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0028 (12 hom.)
• Consequence: OTOGL NM_001378609.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.215
• Publications: 1 publications found

Genes affected

OTOGL (HGNC:26901): (otogelin like) The protein encoded by this gene belongs to the otogelin family. This gene is expressed in the inner ear of vertebrates with the highest level of expression seen at the embryonic stage and lowest in adult. Knockdown studies in zebrafish suggest that this gene is essential for normal inner ear function. Mutations in this gene are associated with autosomal recessive deafness. [provided by RefSeq, Dec 2012]

OTOGL Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 84B

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P
• 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 -17 ACMG points.

• BP6: Variant 12-80352336-T-C is Benign according to our data. Variant chr12-80352336-T-C is described in ClinVar as Benign. ClinVar VariationId is 226955.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.215 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00219 (334/152326) while in subpopulation NFE AF = 0.00297 (202/68022). AF 95% confidence interval is 0.00263. There are 2 homozygotes in GnomAd4. There are 164 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378609.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOGL	NM_001378609.3	MANE Select	c.5307T>C	p.Tyr1769Tyr	synonymous	Exon 45 of 59	NP_001365538.2	Q3ZCN5
	OTOGL	NM_001378610.3		c.5307T>C	p.Tyr1769Tyr	synonymous	Exon 48 of 62	NP_001365539.2	Q3ZCN5
	OTOGL	NM_173591.7		c.5307T>C	p.Tyr1769Tyr	synonymous	Exon 45 of 59	NP_775862.4	Q3ZCN5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOGL	ENST00000547103.7	TSL:5 MANE Select	c.5307T>C	p.Tyr1769Tyr	synonymous	Exon 45 of 59	ENSP00000447211.2	Q3ZCN5
	OTOGL	ENST00000646859.1		c.5172T>C	p.Tyr1724Tyr	synonymous	Exon 49 of 63	ENSP00000496036.1	A0A2R8YF04
	OTOGL	ENST00000298820.7	TSL:5	c.606T>C	p.Tyr202Tyr	synonymous	Exon 6 of 18	ENSP00000298820.3	H7BXL6

Frequencies

GnomAD3 genomes AF: 0.00219 AC: 334 AN: 152208 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00885

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00297

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00302 AC: 739 AN: 244414 AF XY: 0.00310

Gnomad AFR exome AF: 0.000194

Gnomad AMR exome AF: 0.000971

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0103

Gnomad NFE exome AF: 0.00395

Gnomad OTH exome AF: 0.00451

GnomAD4 exome AF: 0.00281 AC: 4100 AN: 1459728 Hom.: 12 Cov.: 31 AF XY: 0.00285 AC XY: 2068 AN XY: 726050

African (AFR) AF: 0.000180 AC: 6 AN: 33414

American (AMR) AF: 0.000924 AC: 41 AN: 44364

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39596

South Asian (SAS) AF: 0.000630 AC: 54 AN: 85772

European-Finnish (FIN) AF: 0.0110 AC: 589 AN: 53350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00294 AC: 3272 AN: 1111112

Other (OTH) AF: 0.00227 AC: 137 AN: 60284

GnomAD4 genome AF: 0.00219 AC: 334 AN: 152326 Hom.: 2 Cov.: 33 AF XY: 0.00220 AC XY: 164 AN XY: 74486

African (AFR) AF: 0.000505 AC: 21 AN: 41580

American (AMR) AF: 0.000654 AC: 10 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00885 AC: 94 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00297 AC: 202 AN: 68022

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00267 Hom.: 0

Bravo AF: 0.00165

EpiCase AF: 0.00224

EpiControl AF: 0.00214

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	2.7
DANN	Benign	0.46
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism

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: rs183555119; hg19: chr12-80746116;