rs7312569

Positions:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001378609.3(OTOGL):c.5512C>G(p.Leu1838Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,600,620 control chromosomes in the GnomAD database, including 30,377 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2751 hom., cov: 33)

Exomes 𝑓: 0.19 ( 27626 hom. )

Consequence

OTOGL
NM_001378609.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.325

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 -16 ACMG points.

BP6

Variant 12-80353429-C-G is Benign according to our data. Variant chr12-80353429-C-G is described in ClinVar as [Benign]. Clinvar id is 226956.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-80353429-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTOGL	NM_001378609.3 linkuse as main transcript	c.5512C>G	p.Leu1838Val	missense_variant	46/59	ENST00000547103.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
OTOGL	ENST00000547103.7 linkuse as main transcript	c.5512C>G	p.Leu1838Val	missense_variant	46/59	5	NM_001378609.3	P1
OTOGL	ENST00000646859.1 linkuse as main transcript	c.5377C>G	p.Leu1793Val	missense_variant	50/63
OTOGL	ENST00000298820.7 linkuse as main transcript	c.814C>G	p.Leu272Val	missense_variant	7/18	5

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28086

AN:

152054

Hom.:

2750

Cov.:

show subpopulations

Gnomad AFR

AF:

0.181

Gnomad AMI

AF:

0.281

Gnomad AMR

AF:

0.215

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.0512

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.107

Gnomad MID

AF:

0.217

Gnomad NFE

AF:

0.199

Gnomad OTH

AF:

0.190

GnomAD3 exomes

AF:

0.176

AC:

40545

AN:

229808

Hom.:

3888

AF XY:

0.179

AC XY:

22249

AN XY:

124084

show subpopulations

Gnomad AFR exome

AF:

0.175

Gnomad AMR exome

AF:

0.200

Gnomad ASJ exome

AF:

0.185

Gnomad EAS exome

AF:

0.0441

Gnomad SAS exome

AF:

0.212

Gnomad FIN exome

AF:

0.104

Gnomad NFE exome

AF:

0.195

Gnomad OTH exome

AF:

0.189

GnomAD4 exome

AF:

0.191

AC:

276908

AN:

1448448

Hom.:

27626

Cov.:

AF XY:

0.192

AC XY:

138055

AN XY:

719156

show subpopulations

Gnomad4 AFR exome

AF:

0.176

Gnomad4 AMR exome

AF:

0.205

Gnomad4 ASJ exome

AF:

0.187

Gnomad4 EAS exome

AF:

0.0385

Gnomad4 SAS exome

AF:

0.208

Gnomad4 FIN exome

AF:

0.110

Gnomad4 NFE exome

AF:

0.199

Gnomad4 OTH exome

AF:

0.187

GnomAD4 genome

AF:

0.185

AC:

28088

AN:

152172

Hom.:

2751

Cov.:

AF XY:

0.182

AC XY:

13508

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.181

Gnomad4 AMR

AF:

0.215

Gnomad4 ASJ

AF:

0.184

Gnomad4 EAS

AF:

0.0513

Gnomad4 SAS

AF:

0.217

Gnomad4 FIN

AF:

0.107

Gnomad4 NFE

AF:

0.199

Gnomad4 OTH

AF:

0.188

Alfa

AF:

0.190

Hom.:

2133

Bravo

AF:

0.192

TwinsUK

AF:

0.193

AC:

714

ALSPAC

AF:

0.199

AC:

767

ESP6500AA

AF:

0.177

AC:

688

ESP6500EA

AF:

0.195

AC:

1621

ExAC

AF:

0.175

AC:

21080

Asia WGS

AF:

0.142

AC:

491

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	Leu1829Val in exon 45 of OTOGL: This variant is not expected to have clinical si gnificance because it has been identified in 19.5% (1621/8296) of European Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs7312569). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.95

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.74

T;.;T

MetaRNN

Benign

0.0041

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.4

.;.;N

REVEL

Benign

0.071

Sift

Benign

0.072

.;.;T

Sift4G

Benign

0.13

.;.;T

Vest4

0.15

MPC

0.024

ClinPred

0.0015

GERP RS

0.45

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.43

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.43

Position offset: -1

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