Variant rs147253069 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_001366057.1(OTUD4):c.3003T>A(p.Ala1001=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00768 in 1,614,062 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0061 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0078 ( 58 hom. )

Consequence

OTUD4
NM_001366057.1 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 1.53

Variant links:

Genes affected

OTUD4 (HGNC:24949): (OTU deubiquitinase 4) Alternatively spliced transcript variants have been found for this gene. The smaller protein isoform encoded by the shorter transcript variant is found only in HIV-1 infected cells. [provided by RefSeq, Jul 2010]

OTUD4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 4-145137772-A-T is Benign according to our data. Variant chr4-145137772-A-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 211809.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=1, Uncertain_significance=1}.

BP7

Synonymous conserved (PhyloP=1.53 with no splicing effect.

BS2

High AC in GnomAd4 at 928 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTUD4	NM_001366057.1 linkuse as main transcript	c.3003T>A	p.Ala1001=	synonymous_variant	21/21	ENST00000447906.8	NP_001352986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTUD4	ENST00000447906.8 linkuse as main transcript	c.3003T>A	p.Ala1001=	synonymous_variant	21/21	5	NM_001366057.1	ENSP00000395487	P1	Q01804-1
OTUD4	ENST00000454497.6 linkuse as main transcript	c.2808T>A	p.Ala936=	synonymous_variant	21/21	2		ENSP00000409279		Q01804-3
OTUD4	ENST00000455611.6 linkuse as main transcript	n.2028+2179T>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00612

AC:

930

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00806

Gnomad ASJ

AF:

0.00491

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.0112

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00848

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00630

AC:

1577

AN:

250442

Hom.:

AF XY:

0.00631

AC XY:

856

AN XY:

135620

show subpopulations

Gnomad AFR exome

AF:

0.00133

Gnomad AMR exome

AF:

0.00445

Gnomad ASJ exome

AF:

0.00397

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00392

Gnomad FIN exome

AF:

0.00924

Gnomad NFE exome

AF:

0.00885

Gnomad OTH exome

AF:

0.00640

GnomAD4 exome

AF:

0.00784

AC:

11464

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00781

AC XY:

5683

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.00499

Gnomad4 ASJ exome

AF:

0.00444

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00407

Gnomad4 FIN exome

AF:

0.00943

Gnomad4 NFE exome

AF:

0.00881

Gnomad4 OTH exome

AF:

0.00664

GnomAD4 genome

AF:

0.00610

AC:

928

AN:

152196

Hom.:

Cov.:

AF XY:

0.00606

AC XY:

451

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00140

Gnomad4 AMR

AF:

0.00805

Gnomad4 ASJ

AF:

0.00491

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00331

Gnomad4 FIN

AF:

0.0112

Gnomad4 NFE

AF:

0.00849

Gnomad4 OTH

AF:

0.00805

Alfa

AF:

0.00717

Hom.:

Bravo

AF:

0.00563

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00894

EpiControl

AF:

0.00806

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2023	OTUD4: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 26, 2018	- -

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jun 27, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

6.1

DANN

Benign

0.63

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