Genetic Variant OTUD6B:p.Gln47Gln (chr8-91071196-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016023.5(OTUD6B):c.141A>G(p.Gln47Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 1,612,418 control chromosomes in the GnomAD database, including 275,730 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 20210 hom., cov: 31)

Exomes 𝑓: 0.59 ( 255520 hom. )

Consequence

OTUD6B
NM_016023.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.532

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 8-91071196-A-G is Benign according to our data. Variant chr8-91071196-A-G is described in ClinVar as [Benign]. Clinvar id is 1259524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.532 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTUD6B	NM_016023.5 link	c.141A>G	p.Gln47Gln	synonymous_variant	Exon 2 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.141A>G	p.Gln47Gln	synonymous_variant	Exon 2 of 7	1	NM_016023.5	ENSP00000384190.4		Q8N6M0-1

Frequencies

GnomAD3 genomes

AF:

0.495

AC:

75080

AN:

151812

Hom.:

20209

Cov.:

show subpopulations

Gnomad AFR

AF:

0.286

Gnomad AMI

AF:

0.625

Gnomad AMR

AF:

0.420

Gnomad ASJ

AF:

0.538

Gnomad EAS

AF:

0.553

Gnomad SAS

AF:

0.668

Gnomad FIN

AF:

0.578

Gnomad MID

AF:

0.582

Gnomad NFE

AF:

0.603

Gnomad OTH

AF:

0.528

GnomAD3 exomes

AF:

0.540

AC:

135535

AN:

250798

Hom.:

38500

AF XY:

0.560

AC XY:

75869

AN XY:

135550

show subpopulations

Gnomad AFR exome

AF:

0.277

Gnomad AMR exome

AF:

0.334

Gnomad ASJ exome

AF:

0.548

Gnomad EAS exome

AF:

0.557

Gnomad SAS exome

AF:

0.653

Gnomad FIN exome

AF:

0.578

Gnomad NFE exome

AF:

0.598

Gnomad OTH exome

AF:

0.571

GnomAD4 exome

AF:

0.586

AC:

856354

AN:

1460488

Hom.:

255520

Cov.:

AF XY:

0.591

AC XY:

429222

AN XY:

726560

show subpopulations

Gnomad4 AFR exome

AF:

0.268

Gnomad4 AMR exome

AF:

0.347

Gnomad4 ASJ exome

AF:

0.545

Gnomad4 EAS exome

AF:

0.550

Gnomad4 SAS exome

AF:

0.651

Gnomad4 FIN exome

AF:

0.578

Gnomad4 NFE exome

AF:

0.603

Gnomad4 OTH exome

AF:

0.582

GnomAD4 genome

AF:

0.494

AC:

75088

AN:

151930

Hom.:

20210

Cov.:

AF XY:

0.496

AC XY:

36832

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.286

Gnomad4 AMR

AF:

0.420

Gnomad4 ASJ

AF:

0.538

Gnomad4 EAS

AF:

0.552

Gnomad4 SAS

AF:

0.667

Gnomad4 FIN

AF:

0.578

Gnomad4 NFE

AF:

0.603

Gnomad4 OTH

AF:

0.531

Alfa

AF:

0.559

Hom.:

12302

Bravo

AF:

0.467

Asia WGS

AF:

0.617

AC:

2144

AN:

3478

EpiCase

AF:

0.602

EpiControl

AF:

0.608

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 14, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.6

DANN

Benign

0.52

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

3.8

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