Genetic Variant OTUD6B:p.Leu16Pro (chr8-91070431-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24933067).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTUD6B	NM_016023.5 link	c.47T>C	p.Leu16Pro	missense_variant	Exon 1 of 7	ENST00000404789.8	NP_057107.4	Q8N6M0-1A0A087X0W9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTUD6B	ENST00000404789.8 link	c.47T>C	p.Leu16Pro	missense_variant	Exon 1 of 7	1	NM_016023.5	ENSP00000384190.4		Q8N6M0-1

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Jan 09, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.137T>C (p.L46P) alteration is located in exon 1 (coding exon 1) of the OTUD6B gene. This alteration results from a T to C substitution at nucleotide position 137, causing the leucine (L) at amino acid position 46 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Uncertain

0.060

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.20

T;T;T

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.23

T;.;T

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Uncertain

0.23

MutationAssessor

Uncertain

2.4

.;.;M

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.0

.;D;.

REVEL

Benign

0.28

Sift

Benign

0.12

.;T;.

Sift4G

Benign

0.30

T;T;T

Polyphen

0.41

.;.;B

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

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

3.1

Varity_R

0.28

gMVP

0.15

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over