Genetic Variant OTUD6B:p.Leu16Pro (chr8-91070431-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_016023.5(OTUD6B):c.47T>C(p.Leu16Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OTUD6B
NM_016023.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.714

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. 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: -0.268 (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=0.24933067).

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.47T>C	p.Leu16Pro	missense	Exon 1 of 7	NP_057107.4
OTUD6B	NM_001416022.1		c.47T>C	p.Leu16Pro	missense	Exon 1 of 6	NP_001402951.1
OTUD6B	NM_001286745.3		c.-397T>C		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.47T>C	p.Leu16Pro	missense	Exon 1 of 7	ENSP00000384190.4	Q8N6M0-1
OTUD6B	ENST00000285420.8	TSL:1	c.137T>C	p.Leu46Pro	missense	Exon 1 of 7	ENSP00000285420.4	A0A087X0W9
OTUD6B	ENST00000617869.4	TSL:1	c.137T>C	p.Leu46Pro	missense	Exon 1 of 7	ENSP00000483706.1	A0A087X0W9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1437700

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

712694

African (AFR)

AF:

0.00

AC:

AN:

33014

American (AMR)

AF:

0.00

AC:

AN:

40234

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25658

East Asian (EAS)

AF:

0.00

AC:

AN:

38712

South Asian (SAS)

AF:

0.00

AC:

AN:

82864

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52096

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1099716

Other (OTH)

AF:

0.00

AC:

AN:

59668

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

Uncertain

0.54

BayesDel_addAF

Uncertain

0.060

BayesDel_noAF

Benign

-0.15

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.20

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.23

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.25

MetaSVM

Uncertain

0.23

MutationAssessor

Uncertain

2.4

PhyloP100

0.71

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.28

Sift

Benign

0.12

Sift4G

Benign

0.30

Polyphen

0.41

Vest4

0.19

MutPred

0.37

Gain of loop (P = 3e-04)

MVP

0.91

MPC

0.025

ClinPred

0.58

GERP RS

3.3

PromoterAI

0.087

Neutral

(source)

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

3.1

Varity_R

0.28

gMVP

0.15

Mutation Taster

=82/18

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over