Variant 20-16748493-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_020157.4(OTOR):c.92T>C(p.Leu31Pro) variant causes a missense change. The variant allele was found at a frequency of 0.183 in 1,608,074 control chromosomes in the GnomAD database, including 29,235 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.16 ( 2164 hom., cov: 33)

Exomes 𝑓: 0.19 ( 27071 hom. )

Consequence

OTOR
NM_020157.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.37

Variant links:

Genes affected

OTOR (HGNC:8517): (otoraplin) This gene encodes a member of the melanoma-inhibiting activity gene family. The encoded protein is secreted via the Golgi apparatus and may function in cartilage development and maintenance. A frequent polymorphism in the translation start codon of this gene can abolish translation and may be associated with forms of deafness. [provided by RefSeq, Jul 2013]

OTOR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002125442).

BP6

Variant 20-16748493-T-C is Benign according to our data. Variant chr20-16748493-T-C is described in ClinVar as [Benign]. Clinvar id is 3060137.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTOR	NM_020157.4 linkuse as main transcript	c.92T>C	p.Leu31Pro	missense_variant	1/4	ENST00000246081.3
OTOR	XM_017027959.3 linkuse as main transcript	c.92T>C	p.Leu31Pro	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTOR	ENST00000246081.3 linkuse as main transcript	c.92T>C	p.Leu31Pro	missense_variant	1/4	1	NM_020157.4	P1

Frequencies

GnomAD3 genomes

AF:

0.155

AC:

23595

AN:

152100

Hom.:

2164

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0699

Gnomad AMI

AF:

0.182

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.174

Gnomad EAS

AF:

0.311

Gnomad SAS

AF:

0.320

Gnomad FIN

AF:

0.172

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.182

Gnomad OTH

AF:

0.149

GnomAD3 exomes

AF:

0.194

AC:

48808

AN:

251196

Hom.:

5405

AF XY:

0.200

AC XY:

27189

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.0687

Gnomad AMR exome

AF:

0.151

Gnomad ASJ exome

AF:

0.180

Gnomad EAS exome

AF:

0.305

Gnomad SAS exome

AF:

0.314

Gnomad FIN exome

AF:

0.178

Gnomad NFE exome

AF:

0.180

Gnomad OTH exome

AF:

0.182

GnomAD4 exome

AF:

0.186

AC:

270621

AN:

1455856

Hom.:

27071

Cov.:

AF XY:

0.190

AC XY:

137540

AN XY:

724658

show subpopulations

Gnomad4 AFR exome

AF:

0.0650

Gnomad4 AMR exome

AF:

0.146

Gnomad4 ASJ exome

AF:

0.177

Gnomad4 EAS exome

AF:

0.307

Gnomad4 SAS exome

AF:

0.312

Gnomad4 FIN exome

AF:

0.182

Gnomad4 NFE exome

AF:

0.178

Gnomad4 OTH exome

AF:

0.185

GnomAD4 genome

AF:

0.155

AC:

23598

AN:

152218

Hom.:

2164

Cov.:

AF XY:

0.157

AC XY:

11685

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0699

Gnomad4 AMR

AF:

0.144

Gnomad4 ASJ

AF:

0.174

Gnomad4 EAS

AF:

0.311

Gnomad4 SAS

AF:

0.320

Gnomad4 FIN

AF:

0.172

Gnomad4 NFE

AF:

0.182

Gnomad4 OTH

AF:

0.149

Alfa

AF:

0.177

Hom.:

6218

Bravo

AF:

0.144

TwinsUK

AF:

0.176

AC:

652

ALSPAC

AF:

0.175

AC:

673

ESP6500AA

AF:

0.0783

AC:

345

ESP6500EA

AF:

0.175

AC:

1503

ExAC

AF:

0.197

AC:

23856

Asia WGS

AF:

0.292

AC:

1013

AN:

3476

EpiCase

AF:

0.173

EpiControl

AF:

0.167

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

OTOR-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.79

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.9

MutationTaster

Benign

7.9e-10

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-5.0

REVEL

Uncertain

0.45

Sift

Uncertain

0.014

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.30

MPC

0.36

ClinPred

0.017

GERP RS

5.9

Varity_R

0.91

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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