dbSNP rs745687110: OTUD6B:p.Trp10Arg (chr8-91070322-T-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 3P and 4B. PM2PP2BP4_ModerateBP6_Moderate

The ENST00000285420.8(OTUD6B):c.28T>A(p.Trp10Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

OTUD6B
ENST00000285420.8 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.68

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: Likely_benign. The variant received -1 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: -0.53276 (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=0.1902782).

BP6

Variant 8-91070322-T-A is Benign according to our data. Variant chr8-91070322-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3412773.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000285420.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OTUD6B	NM_016023.5	MANE Select	c.-63T>A	upstream_gene	N/A	NP_057107.4
OTUD6B	NM_001416022.1		c.-63T>A	upstream_gene	N/A	NP_001402951.1
OTUD6B	NM_001286745.3		c.-506T>A	upstream_gene	N/A	NP_001273674.1	Q8N6M0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OTUD6B	ENST00000285420.8	TSL:1	c.28T>A	p.Trp10Arg	missense	Exon 1 of 7	ENSP00000285420.4	A0A087X0W9
OTUD6B	ENST00000617869.4	TSL:1	c.28T>A	p.Trp10Arg	missense	Exon 1 of 7	ENSP00000483706.1	A0A087X0W9
OTUD6B	ENST00000910621.1		c.-63T>A		5_prime_UTR	Exon 1 of 7	ENSP00000580680.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460080

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726122

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33460

American (AMR)

AF:

0.00

AC:

AN:

44512

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26084

East Asian (EAS)

AF:

0.00

AC:

AN:

39630

South Asian (SAS)

AF:

0.00

AC:

AN:

85946

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53260

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5588

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111326

Other (OTH)

AF:

0.00

AC:

AN:

60274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.013

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.35

M_CAP

Benign

0.028

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.86

PhyloP100

1.7

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.12

REVEL

Benign

0.055

Sift

Benign

0.034

Sift4G

Uncertain

0.034

Vest4

0.25

MutPred

0.45

Gain of disorder (P = 0.0014)

MVP

0.43

MPC

0.023

ClinPred

0.56

GERP RS

5.7

PromoterAI

0.089

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.11

Mutation Taster

=85/15

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over