NM_001378609.3:c.4082-409G>A

Variant names:

• chr12-80323314-G-A
• rs17249026
• NM_001378609.3:c.4082-409G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378609.3(OTOGL):​c.4082-409G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0527 in 152,154 control chromosomes in the GnomAD database, including 292 homozygotes. 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 0.053 (292 hom., cov: 32)
• Consequence: OTOGL NM_001378609.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• 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: Laboratory for Molecular Medicine, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOGL	NM_001378609.3	c.4082-409G>A		intron_variant	Intron 34 of 58	ENST00000547103.7	NP_001365538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTOGL	ENST00000547103.7	c.4082-409G>A		intron_variant	Intron 34 of 58	5	NM_001378609.3	ENSP00000447211.2
OTOGL	ENST00000646859.1	c.3947-409G>A		intron_variant	Intron 38 of 62			ENSP00000496036.1

Frequencies

GnomAD3 genomes AF: 0.0527 AC: 8014 AN: 152036 Hom.: 290 Cov.: 32

Gnomad AFR AF: 0.0208

Gnomad AMI AF: 0.0604

Gnomad AMR AF: 0.0564

Gnomad ASJ AF: 0.0955

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0535

Gnomad FIN AF: 0.0273

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0762

Gnomad OTH AF: 0.0616

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0527 AC: 8022 AN: 152154 Hom.: 292 Cov.: 32 AF XY: 0.0499 AC XY: 3713 AN XY: 74388

African (AFR) AF: 0.0211 AC: 874 AN: 41512

American (AMR) AF: 0.0563 AC: 861 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0955 AC: 331 AN: 3466

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.0539 AC: 260 AN: 4822

European-Finnish (FIN) AF: 0.0273 AC: 288 AN: 10566

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0762 AC: 5179 AN: 68004

Other (OTH) AF: 0.0605 AC: 128 AN: 2116

Alfa AF: 0.0623 Hom.: 44

Bravo AF: 0.0529

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.085
DANN	Benign	0.23
PhyloP100		-1.2
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: rs17249026; hg19: chr12-80717094;