Variant 15-31483818-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001382637.1(OTUD7A):c.2278A>G(p.Ser760Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.991 in 1,003,664 control chromosomes in the GnomAD database, including 492,514 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.99 ( 71836 hom., cov: 27)

Exomes 𝑓: 0.99 ( 420678 hom. )

Consequence

OTUD7A
NM_001382637.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0740

Variant links:

Genes affected

OTUD7A (HGNC:20718): (OTU deubiquitinase 7A) The protein encoded by this gene is a deubiquitinizing enzyme and possible tumor suppressor. The encoded protein acts on TNF receptor associated factor 6 (TRAF6) to control nuclear factor kappa B expression. However, this gene is downregulated by SNAIL1 in hepatocellular carcinoma cells, contributing to their progression and malignancy. [provided by RefSeq, Aug 2016]

OTUD7A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.964613E-7).

BP6

Variant 15-31483818-T-C is Benign according to our data. Variant chr15-31483818-T-C is described in ClinVar as [Benign]. Clinvar id is 1242878.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTUD7A	NM_001382637.1 link	c.2278A>G	p.Ser760Gly	missense_variant	13/13	ENST00000307050.6	NP_001369566.1
OTUD7A	NM_130901.3 link	c.2257A>G	p.Ser753Gly	missense_variant	14/14		NP_570971.1	Q8TE49-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OTUD7A	ENST00000307050.6 link	c.2278A>G	p.Ser760Gly	missense_variant	13/13	1	NM_001382637.1	ENSP00000305926.5	Q8TE49-2
OTUD7A	ENST00000560598.2 link	c.2257A>G	p.Ser753Gly	missense_variant	14/14	5		ENSP00000453883.2	Q8TE49-1H0YN66
OTUD7A	ENST00000678495.1 link	c.2257A>G	p.Ser753Gly	missense_variant	11/11			ENSP00000503326.1	Q8TE49-1

Frequencies

GnomAD3 genomes

AF:

0.994

AC:

144370

AN:

145172

Hom.:

71786

Cov.:

show subpopulations

Gnomad AFR

AF:

0.999

Gnomad AMI

AF:

0.999

Gnomad AMR

AF:

0.997

Gnomad ASJ

AF:

0.997

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.997

Gnomad FIN

AF:

0.991

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

0.991

Gnomad OTH

AF:

0.997

GnomAD3 exomes

AF:

0.991

AC:

212

AN:

214

Hom.:

105

AF XY:

0.984

AC XY:

120

AN XY:

122

show subpopulations

Gnomad NFE exome

AF:

0.990

Gnomad OTH exome

AF:

1.00

GnomAD4 exome

AF:

0.990

AC:

849823

AN:

858392

Hom.:

420678

Cov.:

AF XY:

0.990

AC XY:

394913

AN XY:

398918

show subpopulations

Gnomad4 AFR exome

AF:

0.999

Gnomad4 AMR exome

AF:

0.998

Gnomad4 ASJ exome

AF:

0.996

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.994

Gnomad4 FIN exome

AF:

0.990

Gnomad4 NFE exome

AF:

0.990

Gnomad4 OTH exome

AF:

0.992

GnomAD4 genome

AF:

0.994

AC:

144470

AN:

145272

Hom.:

71836

Cov.:

AF XY:

0.995

AC XY:

70253

AN XY:

70624

show subpopulations

Gnomad4 AFR

AF:

0.999

Gnomad4 AMR

AF:

0.997

Gnomad4 ASJ

AF:

0.997

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.997

Gnomad4 FIN

AF:

0.991

Gnomad4 NFE

AF:

0.991

Gnomad4 OTH

AF:

0.997

Alfa

AF:

0.991

Hom.:

9097

Bravo

AF:

0.995

TwinsUK

AF:

0.997

AC:

3697

ALSPAC

AF:

0.997

AC:

3842

ExAC

AF:

1.00

AC:

Asia WGS

AF:

0.997

AC:

2216

AN:

2222

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 02, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

OTUD7A-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 12, 2021

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

Benign

0.045

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.74

CADD

Benign

4.8

DANN

Benign

0.30

DEOGEN2

Benign

0.017

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0018

LIST_S2

Benign

0.14

MetaRNN

Benign

0.0000010

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.65

REVEL

Benign

0.027

Sift

Benign

0.26

Sift4G

Benign

0.56

Polyphen

0.0

Vest4

0.044

ClinPred

0.061

GERP RS

1.5

Varity_R

0.051

gMVP

0.35

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