rs35397172

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBS1BS2

The NM_001378609.3(OTOGL):c.6204A>G(p.Gln2068=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000716 in 1,610,840 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 9 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 8 hom. )

Consequence

OTOGL
NM_001378609.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0650

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 -15 ACMG points.

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant 12-80358753-A-G is Benign according to our data. Variant chr12-80358753-A-G is described in ClinVar as [Benign]. Clinvar id is 226965.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00356 (543/152320) while in subpopulation AFR AF= 0.0125 (518/41574). AF 95% confidence interval is 0.0116. There are 9 homozygotes in gnomad4. There are 278 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTOGL	NM_001378609.3 linkuse as main transcript	c.6204A>G	p.Gln2068=	synonymous_variant	51/59	ENST00000547103.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTOGL	ENST00000547103.7 linkuse as main transcript	c.6204A>G	p.Gln2068=	synonymous_variant	51/59	5	NM_001378609.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00354

AC:

539

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0124

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000893

AC:

221

AN:

247586

Hom.:

AF XY:

0.000754

AC XY:

101

AN XY:

134022

show subpopulations

Gnomad AFR exome

AF:

0.0117

Gnomad AMR exome

AF:

0.000697

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000272

Gnomad OTH exome

AF:

0.000657

GnomAD4 exome

AF:

0.000419

AC:

611

AN:

1458520

Hom.:

Cov.:

AF XY:

0.000360

AC XY:

261

AN XY:

725748

show subpopulations

Gnomad4 AFR exome

AF:

0.0140

Gnomad4 AMR exome

AF:

0.000985

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000261

Gnomad4 OTH exome

AF:

0.00103

GnomAD4 genome

AF:

0.00356

AC:

543

AN:

152320

Hom.:

Cov.:

AF XY:

0.00373

AC XY:

278

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0125

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000931

Hom.:

Bravo

AF:

0.00414

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000594

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 28, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 28, 2020	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Nov 24, 2014

Gln2059Gln in exon 50 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 1.1% (47/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs35397172). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

Cadd

Benign

Dann

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.64

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.64

Position offset: -5

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