Variant chr20-16748403-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 8P and 16B. PVS1BP6_Very_StrongBS1BS2

The NM_020157.4(OTOR):c.2T>C(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.0392 in 1,602,702 control chromosomes in the GnomAD database, including 1,395 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 101 hom., cov: 32)

Exomes 𝑓: 0.040 ( 1294 hom. )

Consequence

OTOR
NM_020157.4 start_lost

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.17

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 -8 ACMG points.

PVS1

Start lost variant, no new inframe start found.

BP6

Variant 20-16748403-T-C is Benign according to our data. Variant chr20-16748403-T-C is described in ClinVar as [Benign]. Clinvar id is 403282.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-16748403-T-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0319 (4852/152252) while in subpopulation NFE AF= 0.0447 (3037/68012). AF 95% confidence interval is 0.0433. There are 101 homozygotes in gnomad4. There are 2409 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 101 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTOR	NM_020157.4 linkuse as main transcript	c.2T>C	p.Met1?	start_lost	1/4	ENST00000246081.3
OTOR	XM_017027959.3 linkuse as main transcript	c.2T>C	p.Met1?	start_lost	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTOR	ENST00000246081.3 linkuse as main transcript	c.2T>C	p.Met1?	start_lost	1/4	1	NM_020157.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0319

AC:

4854

AN:

152134

Hom.:

101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00862

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.0288

Gnomad ASJ

AF:

0.0625

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0224

Gnomad FIN

AF:

0.0513

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0446

Gnomad OTH

AF:

0.0358

GnomAD3 exomes

AF:

0.0348

AC:

8743

AN:

251144

Hom.:

191

AF XY:

0.0358

AC XY:

4857

AN XY:

135716

show subpopulations

Gnomad AFR exome

AF:

0.00745

Gnomad AMR exome

AF:

0.0163

Gnomad ASJ exome

AF:

0.0651

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.0249

Gnomad FIN exome

AF:

0.0540

Gnomad NFE exome

AF:

0.0463

Gnomad OTH exome

AF:

0.0340

GnomAD4 exome

AF:

0.0399

AC:

57945

AN:

1450450

Hom.:

1294

Cov.:

AF XY:

0.0403

AC XY:

29086

AN XY:

722410

show subpopulations

Gnomad4 AFR exome

AF:

0.00734

Gnomad4 AMR exome

AF:

0.0169

Gnomad4 ASJ exome

AF:

0.0636

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0246

Gnomad4 FIN exome

AF:

0.0518

Gnomad4 NFE exome

AF:

0.0435

Gnomad4 OTH exome

AF:

0.0374

GnomAD4 genome

AF:

0.0319

AC:

4852

AN:

152252

Hom.:

101

Cov.:

AF XY:

0.0324

AC XY:

2409

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00859

Gnomad4 AMR

AF:

0.0287

Gnomad4 ASJ

AF:

0.0625

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0228

Gnomad4 FIN

AF:

0.0513

Gnomad4 NFE

AF:

0.0447

Gnomad4 OTH

AF:

0.0354

Alfa

AF:

0.0429

Hom.:

308

Bravo

AF:

0.0283

TwinsUK

AF:

0.0442

AC:

164

ALSPAC

AF:

0.0439

AC:

169

ESP6500AA

AF:

0.00908

AC:

ESP6500EA

AF:

0.0453

AC:

390

ExAC

AF:

0.0352

AC:

4269

Asia WGS

AF:

0.0120

AC:

AN:

3476

EpiCase

AF:

0.0497

EpiControl

AF:

0.0456

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all):430/13006=3.3% -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.0043

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

PROVEAN

Benign

-0.90

REVEL

Benign

0.21

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0080

Polyphen

0.96

Vest4

0.34

ClinPred

0.037

GERP RS

5.9

Varity_R

0.66

gMVP

0.83

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