Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001378609.3(OTOGL):c.1582G>A(p.Glu528Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OTOGL
NM_001378609.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.27

Publications

0 publications found

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 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

OTOGL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41702104).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378609.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
OTOGL	NM_001378609.3	MANE Select	c.1582G>A	p.Glu528Lys	missense	Exon 16 of 59	NP_001365538.2
OTOGL	NM_001378610.3		c.1582G>A	p.Glu528Lys	missense	Exon 19 of 62	NP_001365539.2
OTOGL	NM_173591.7		c.1582G>A	p.Glu528Lys	missense	Exon 16 of 59	NP_775862.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
OTOGL	ENST00000547103.7	TSL:5 MANE Select	c.1582G>A	p.Glu528Lys	missense	Exon 16 of 59	ENSP00000447211.2
OTOGL	ENST00000646859.1		c.1582G>A	p.Glu528Lys	missense	Exon 21 of 63	ENSP00000496036.1
OTOGL	ENST00000643417.1		n.2242G>A		non_coding_transcript_exon	Exon 19 of 23

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1348522

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

664496

African (AFR)

AF:

0.00

AC:

AN:

29144

American (AMR)

AF:

0.00

AC:

AN:

23236

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21690

East Asian (EAS)

AF:

0.00

AC:

AN:

36332

South Asian (SAS)

AF:

0.00

AC:

AN:

67328

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47066

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5380

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1062816

Other (OTH)

AF:

0.00

AC:

AN:

55530

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.051

MetaRNN

Benign

0.42

MetaSVM

Benign

-0.47

PhyloP100

5.3

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.5

REVEL

Benign

0.17

Sift

Benign

0.081

Sift4G

Benign

0.16

Vest4

0.26

MutPred

0.62

Gain of methylation at E519 (P = 0.0017)

MVP

0.64

MPC

0.027

ClinPred

0.59

GERP RS

5.5

gMVP

0.43

Mutation Taster

=79/21

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs876657942

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over