Variant chr20-16748891-A-G 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_020157.4(OTOR):c.140A>G(p.Gln47Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00009 in 1,599,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000078 ( 0 hom. )

Consequence

OTOR
NM_020157.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.49

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 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=0.106934726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTOR	NM_020157.4 linkuse as main transcript	c.140A>G	p.Gln47Arg	missense_variant	2/4	ENST00000246081.3
OTOR	XM_017027959.3 linkuse as main transcript	c.140A>G	p.Gln47Arg	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTOR	ENST00000246081.3 linkuse as main transcript	c.140A>G	p.Gln47Arg	missense_variant	2/4	1	NM_020157.4	P1

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000802

AC:

AN:

237052

Hom.:

AF XY:

0.0000701

AC XY:

AN XY:

128340

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000228

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:

0.000110

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000781

AC:

113

AN:

1447376

Hom.:

Cov.:

AF XY:

0.0000722

AC XY:

AN XY:

719742

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000195

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000912

Gnomad4 OTH exome

AF:

0.0000670

GnomAD4 genome

AF:

0.000204

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000141

Hom.:

Bravo

AF:

0.000212

ExAC

AF:

0.0000741

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0055

Eigen

Benign

-0.095

Eigen_PC

Benign

0.094

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.54

M_CAP

Benign

0.0095

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.60

MutationTaster

Benign

0.93

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.71

REVEL

Benign

0.10

Sift

Uncertain

0.016

Sift4G

Benign

0.14

Polyphen

0.32

Vest4

0.32

MVP

0.32

MPC

0.047

ClinPred

0.069

GERP RS

5.7

Varity_R

0.20

gMVP

0.59

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