rs758606974

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_016023.5(OTUD6B):c.43C>G(p.Leu15Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000452 in 1,593,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

OTUD6B
NM_016023.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 1.82

Publications

0 publications found

Variant links:

Genes affected

OTUD6B (HGNC:24281): (OTU deubiquitinase 6B) This gene encodes a member of the ovarian tumor domain (OTU)-containing subfamily of deubiquitinating enzymes. Deubiquitinating enzymes are primarily involved in removing ubiquitin from proteins targeted for degradation. This protein may function as a negative regulator of the cell cycle in B cells. [provided by RefSeq, Nov 2013]

OTUD6B links:

OTUD6B-AS1 (HGNC:50466): (OTUD6B antisense RNA 1 (head to head))

OTUD6B-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 4 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.29632 (below the threshold of 3.09). Trascript score misZ: -0.268 (below the threshold of 3.09). GenCC associations: The gene is linked to intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies.

BP4

Computational evidence support a benign effect (MetaRNN=0.3976066).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016023.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OTUD6B	NM_016023.5	MANE Select	c.43C>G	p.Leu15Val	missense	Exon 1 of 7	NP_057107.4
OTUD6B	NM_001416022.1		c.43C>G	p.Leu15Val	missense	Exon 1 of 6	NP_001402951.1
OTUD6B	NM_001286745.3		c.-401C>G		5_prime_UTR	Exon 1 of 8	NP_001273674.1	Q8N6M0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OTUD6B	ENST00000404789.8	TSL:1 MANE Select	c.43C>G	p.Leu15Val	missense	Exon 1 of 7	ENSP00000384190.4	Q8N6M0-1
OTUD6B	ENST00000285420.8	TSL:1	c.133C>G	p.Leu45Val	missense	Exon 1 of 7	ENSP00000285420.4	A0A087X0W9
OTUD6B	ENST00000617869.4	TSL:1	c.133C>G	p.Leu45Val	missense	Exon 1 of 7	ENSP00000483706.1	A0A087X0W9

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.0000735

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000329

AC:

AN:

212538

AF XY:

0.0000439

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000517

Gnomad NFE exome

AF:

0.0000643

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000437

AC:

AN:

1440990

Hom.:

Cov.:

AF XY:

0.0000448

AC XY:

AN XY:

714646

show subpopulations

African (AFR)

AF:

0.0000302

AC:

AN:

33096

American (AMR)

AF:

0.0000245

AC:

AN:

40734

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25718

East Asian (EAS)

AF:

0.00

AC:

AN:

38914

South Asian (SAS)

AF:

0.0000120

AC:

AN:

83282

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52288

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.0000499

AC:

AN:

1101428

Other (OTH)

AF:

0.0000836

AC:

AN:

59792

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000592

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41426

American (AMR)

AF:

0.000196

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68022

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

OTUD6B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Uncertain

0.068

BayesDel_noAF

Uncertain

0.040

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.030

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.59

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.40

MetaSVM

Uncertain

0.74

MutationAssessor

Benign

1.9

PhyloP100

1.8

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.52

Sift

Benign

0.30

Sift4G

Benign

0.27

Polyphen

1.0

Vest4

0.44

MutPred

0.37

Gain of MoRF binding (P = 0.0824)

MVP

0.92

MPC

0.14

ClinPred

0.59

GERP RS

4.8

PromoterAI

-0.037

Neutral

(source)

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Varity_R

0.51

gMVP

0.13

Mutation Taster

=259/41

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over