Variant 12-80210882-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001378609.3(OTOGL):c.115T>C(p.Ser39Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000225 in 1,331,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 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: 0.0000023 ( 0 hom. )

Consequence

OTOGL
NM_001378609.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.194

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15619364).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTOGL	NM_001378609.3 linkuse as main transcript	c.115T>C	p.Ser39Pro	missense_variant	3/59	ENST00000547103.7	NP_001365538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
OTOGL	ENST00000547103.7 linkuse as main transcript	c.115T>C	p.Ser39Pro	missense_variant	3/59	5	NM_001378609.3	ENSP00000447211	P1
OTOGL	ENST00000646859.1 linkuse as main transcript	c.115T>C	p.Ser39Pro	missense_variant	8/63			ENSP00000496036
OTOGL	ENST00000643417.1 linkuse as main transcript	n.775T>C		non_coding_transcript_exon_variant	6/23

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000175

AC:

AN:

114006

Hom.:

AF XY:

0.0000159

AC XY:

AN XY:

62846

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:

0.000105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000225

AC:

AN:

1331286

Hom.:

Cov.:

AF XY:

0.00000304

AC XY:

AN XY:

657426

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000413

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000679

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2022

The c.88T>C (p.S30P) alteration is located in exon 2 (coding exon 2) of the OTOGL gene. This alteration results from a T to C substitution at nucleotide position 88, causing the serine (S) at amino acid position 30 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.41

T;.;T

M_CAP

Benign

0.0072

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.4

.;.;N

REVEL

Benign

0.020

Sift

Benign

0.15

.;.;T

Sift4G

Pathogenic

0.0

.;.;D

Vest4

0.28

MutPred

0.26

.;.;Gain of relative solvent accessibility (P = 0.09);

MVP

0.13

MPC

0.025

ClinPred

0.56

GERP RS

3.3

gMVP

0.31

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over