12-80209626-A-T

Variant names:

• chr12-80209626-A-T
• rs4842344
• NM_001378609.3:c.79+116A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378609.3(OTOGL):​c.79+116A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 582,352 control chromosomes in the GnomAD database, including 66,525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (14841 hom., cov: 32)
  • Exomes 𝑓: 0.48 (51684 hom.)
• Consequence: OTOGL NM_001378609.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.938
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 12-80209626-A-T is Benign according to our data. Variant chr12-80209626-A-T is described in ClinVar as Benign. ClinVar VariationId is 1274148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

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.79+116A>T		intron	N/A	NP_001365538.2	Q3ZCN5
	OTOGL	NM_001378610.3		c.79+116A>T		intron	N/A	NP_001365539.2	Q3ZCN5
	OTOGL	NM_173591.7		c.79+116A>T		intron	N/A	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.79+116A>T		intron	N/A	ENSP00000447211.2	Q3ZCN5
	OTOGL	ENST00000646859.1		c.79+116A>T		intron	N/A	ENSP00000496036.1	A0A2R8YF04
	OTOGL	ENST00000643417.1		n.739+116A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61443 AN: 151910 Hom.: 14837 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.415

GnomAD4 exome AF: 0.484 AC: 208173 AN: 430320 Hom.: 51684 AF XY: 0.486 AC XY: 109081 AN XY: 224556

African (AFR) AF: 0.116 AC: 1408 AN: 12176

American (AMR) AF: 0.613 AC: 9713 AN: 15852

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 5317 AN: 12556

East Asian (EAS) AF: 0.380 AC: 10876 AN: 28646

South Asian (SAS) AF: 0.513 AC: 14033 AN: 27358

European-Finnish (FIN) AF: 0.515 AC: 12710 AN: 24666

Middle Eastern (MID) AF: 0.384 AC: 703 AN: 1830

European-Non Finnish (NFE) AF: 0.502 AC: 142132 AN: 283182

Other (OTH) AF: 0.469 AC: 11281 AN: 24054

GnomAD4 genome AF: 0.404 AC: 61454 AN: 152032 Hom.: 14841 Cov.: 32 AF XY: 0.407 AC XY: 30260 AN XY: 74302

African (AFR) AF: 0.125 AC: 5195 AN: 41520

American (AMR) AF: 0.559 AC: 8526 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1482 AN: 3468

East Asian (EAS) AF: 0.407 AC: 2102 AN: 5168

South Asian (SAS) AF: 0.510 AC: 2457 AN: 4814

European-Finnish (FIN) AF: 0.510 AC: 5378 AN: 10536

Middle Eastern (MID) AF: 0.441 AC: 128 AN: 290

European-Non Finnish (NFE) AF: 0.515 AC: 34983 AN: 67956

Other (OTH) AF: 0.414 AC: 873 AN: 2108

Alfa AF: 0.458 Hom.: 2175

Bravo AF: 0.392

Asia WGS AF: 0.461 AC: 1593 AN: 3450

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.94
DANN	Benign	0.78
PhyloP100		-0.94
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: rs4842344; hg19: chr12-80603406; COSMIC: COSV72007592;