chr12-80302639-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_001378609.3(OTOGL):c.3069A>G(p.Gln1023Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000917 in 1,366,972 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00078 ( 4 hom. )

Consequence

OTOGL
NM_001378609.3 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: 0.181

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 12-80302639-A-G is Benign according to our data. Variant chr12-80302639-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 226936.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Benign=2, Uncertain_significance=1}. Variant chr12-80302639-A-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.181 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.002 (304/152322) while in subpopulation AFR AF= 0.00443 (184/41560). AF 95% confidence interval is 0.0039. There are 0 homozygotes in gnomad4. There are 140 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOGL	NM_001378609.3 link	c.3069A>G	p.Gln1023Gln	synonymous_variant	Exon 28 of 59	ENST00000547103.7	NP_001365538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTOGL	ENST00000547103.7 link	c.3069A>G	p.Gln1023Gln	synonymous_variant	Exon 28 of 59	5	NM_001378609.3	ENSP00000447211.2		Q3ZCN5
OTOGL	ENST00000646859.1 link	c.2934A>G	p.Gln978Gln	synonymous_variant	Exon 32 of 63			ENSP00000496036.1		A0A2R8YF04

Frequencies

GnomAD3 genomes

AF:

0.00198

AC:

301

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00432

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00340

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000779

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00102

AC:

AN:

78356

Hom.:

AF XY:

0.000996

AC XY:

AN XY:

43192

show subpopulations

Gnomad AFR exome

AF:

0.00364

Gnomad AMR exome

AF:

0.00225

Gnomad ASJ exome

AF:

0.000642

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000874

Gnomad OTH exome

AF:

0.00433

GnomAD4 exome

AF:

0.000782

AC:

950

AN:

1214650

Hom.:

Cov.:

AF XY:

0.000771

AC XY:

453

AN XY:

587768

show subpopulations

Gnomad4 AFR exome

AF:

0.00558

Gnomad4 AMR exome

AF:

0.00310

Gnomad4 ASJ exome

AF:

0.000665

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000805

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000598

Gnomad4 OTH exome

AF:

0.00231

GnomAD4 genome

AF:

0.00200

AC:

304

AN:

152322

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

140

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00443

Gnomad4 AMR

AF:

0.00333

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000779

Gnomad4 OTH

AF:

0.00522

Alfa

AF:

0.00163

Hom.:

Bravo

AF:

0.00228

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:3

Jan 07, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

OTOGL: BP4, BP7 -

Jan 12, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 01, 2018

Eurofins Ntd Llc (ga)

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Gln1014Gln in exon 27 of OTOGL: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 4.6% (9/194) of Lu hya (Kenyan) chromosomes from a broad population by the 1000 Genomes Project (ht tp://www.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs144125797). -

OTOGL-related disorder

Benign:1

Mar 18, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.7

DANN

Benign

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over