Variant 8-91070335-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000285420.8(OTUD6B):c.41C>T(p.Thr14Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,613,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

OTUD6B
ENST00000285420.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.23

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=0.07601833).

Transcripts

RefSeq

Gene	Transcript	Effect	MANE
OTUD6B	NM_016023.5 linkuse as main transcript	upstream_gene_variant	ENST00000404789.8
OTUD6B	NM_001286745.3 linkuse as main transcript	upstream_gene_variant
OTUD6B	NM_001416022.1 linkuse as main transcript	upstream_gene_variant
OTUD6B	XM_047421864.1 linkuse as main transcript	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTUD6B	ENST00000404789.8 linkuse as main transcript			upstream_gene_variant		1	NM_016023.5		Q8N6M0-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248182

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134424

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000893

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000890

AC:

AN:

1460938

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726666

show subpopulations

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 10, 2022

The c.41C>T (p.T14I) alteration is located in exon 1 (coding exon 1) of the OTUD6B gene. This alteration results from a C to T substitution at nucleotide position 41, causing the threonine (T) at amino acid position 14 to be replaced by an isoleucine (I). 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

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.3

DANN

Benign

0.81

DEOGEN2

Benign

0.0064

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.33

T;.

M_CAP

Benign

0.0090

MetaRNN

Benign

0.076

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.19

.;N

REVEL

Benign

0.016

Sift

Benign

0.25

.;T

Sift4G

Benign

0.073

T;T

Vest4

0.16

MutPred

0.30

Loss of loop (P = 0.0512);Loss of loop (P = 0.0512);

MVP

0.072

MPC

0.018

ClinPred

0.10

GERP RS

-3.1

gMVP

0.048

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