12-80209639-A-G

Variant names:

• chr12-80209639-A-G
• rs1244909
• NM_001378609.3:c.79+129A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001378609.3(OTOGL):​c.79+129A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 490,608 control chromosomes in the GnomAD database, including 470 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.038 (365 hom., cov: 32)
  • Exomes 𝑓: 0.0053 (105 hom.)
• Consequence: OTOGL NM_001378609.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.637
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 12-80209639-A-G is Benign according to our data. Variant chr12-80209639-A-G is described in ClinVar as [Benign]. Clinvar id is 1178823.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOGL	NM_001378609.3	c.79+129A>G		intron_variant	Intron 2 of 58	ENST00000547103.7	NP_001365538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTOGL	ENST00000547103.7	c.79+129A>G		intron_variant	Intron 2 of 58	5	NM_001378609.3	ENSP00000447211.2
OTOGL	ENST00000646859.1	c.79+129A>G		intron_variant	Intron 7 of 62			ENSP00000496036.1
OTOGL	ENST00000643417.1	n.739+129A>G		intron_variant	Intron 5 of 22

Frequencies

GnomAD3 genomes AF: 0.0374 AC: 5695 AN: 152120 Hom.: 361 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0140

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.0239

GnomAD4 exome AF: 0.00533 AC: 1803 AN: 338370 Hom.: 105 AF XY: 0.00480 AC XY: 834 AN XY: 173920

African (AFR) AF: 0.135 AC: 1318 AN: 9786

American (AMR) AF: 0.00824 AC: 91 AN: 11044

Ashkenazi Jewish (ASJ) AF: 0.000378 AC: 4 AN: 10582

East Asian (EAS) AF: 0.00 AC: 0 AN: 25558

South Asian (SAS) AF: 0.000457 AC: 6 AN: 13134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21068

Middle Eastern (MID) AF: 0.0102 AC: 15 AN: 1470

European-Non Finnish (NFE) AF: 0.000566 AC: 128 AN: 226094

Other (OTH) AF: 0.0123 AC: 241 AN: 19634

GnomAD4 genome AF: 0.0376 AC: 5717 AN: 152238 Hom.: 365 Cov.: 32 AF XY: 0.0358 AC XY: 2669 AN XY: 74456

African (AFR) AF: 0.130 AC: 5410 AN: 41538

American (AMR) AF: 0.0140 AC: 214 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00690 AC: 2 AN: 290

European-Non Finnish (NFE) AF: 0.000603 AC: 41 AN: 68010

Other (OTH) AF: 0.0237 AC: 50 AN: 2114

Alfa AF: 0.0337 Hom.: 34

Bravo AF: 0.0433

Asia WGS AF: 0.0110 AC: 39 AN: 3452

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.46
DANN	Benign	0.74
PhyloP100		-0.64
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: rs1244909; hg19: chr12-80603419;