Variant 12-80219820-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong

The NM_001378609.3(OTOGL):c.242G>T(p.Cys81Phe) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C81Y) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OTOGL
NM_001378609.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.97

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 Uncertain_significance. Variant got 4 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.945

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTOGL	NM_001378609.3 linkuse as main transcript	c.242G>T	p.Cys81Phe	missense_variant	6/59	ENST00000547103.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
OTOGL	ENST00000547103.7 linkuse as main transcript	c.242G>T	p.Cys81Phe	missense_variant	6/59	5	NM_001378609.3	P1
OTOGL	ENST00000646859.1 linkuse as main transcript	c.242G>T	p.Cys81Phe	missense_variant	11/63
OTOGL	ENST00000643417.1 linkuse as main transcript	n.902G>T		non_coding_transcript_exon_variant	9/23

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

146614

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000259

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000461

AC:

AN:

216742

Hom.:

AF XY:

0.00000846

AC XY:

AN XY:

118272

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000978

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000143

AC:

AN:

1401634

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

698962

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000243

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000682

AC:

AN:

146698

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71324

show subpopulations

Gnomad4 AFR

AF:

0.0000258

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.70

T;.;T

M_CAP

Uncertain

0.096

MetaRNN

Pathogenic

0.94

D;D;D

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.66

Vest4

0.86

MutPred

0.88

.;.;Gain of ubiquitination at K69 (P = 0.0701);

MVP

0.18

MPC

0.21

ClinPred

0.97

GERP RS

6.0

gMVP

0.89

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over