8-91070370-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The ENST00000285420.8(OTUD6B):c.76G>A(p.Gly26Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00233 in 1,612,012 control chromosomes in the GnomAD database, including 11 homozygotes. 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 11 hom. )

Consequence

OTUD6B
ENST00000285420.8 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.105

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 Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051209033).

BP6

Variant 8-91070370-G-A is Benign according to our data. Variant chr8-91070370-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1033385.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0013 (198/152286) while in subpopulation NFE AF= 0.00219 (149/68018). AF 95% confidence interval is 0.0019. There are 0 homozygotes in gnomad4. There are 90 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
OTUD6B	NM_016023.5 link	c.-15G>A	5_prime_UTR_variant	Exon 1 of 7	ENST00000404789.8	NP_057107.4	Q8N6M0-1A0A087X0W9
OTUD6B	NM_001416022.1 link	c.-15G>A	5_prime_UTR_variant	Exon 1 of 6		NP_001402951.1
OTUD6B	NM_001286745.3 link	c.-458G>A	5_prime_UTR_variant	Exon 1 of 8		NP_001273674.1	Q8N6M0-2
OTUD6B	XM_047421864.1 link	c.-15G>A	5_prime_UTR_variant	Exon 1 of 4		XP_047277820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTUD6B	ENST00000404789 link	c.-15G>A		5_prime_UTR_variant	Exon 1 of 7	1	NM_016023.5	ENSP00000384190.4		Q8N6M0-1

Frequencies

GnomAD3 genomes

AF:

0.00130

AC:

198

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00219

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00133

AC:

328

AN:

245972

Hom.:

AF XY:

0.00150

AC XY:

199

AN XY:

132998

show subpopulations

Gnomad AFR exome

AF:

0.000509

Gnomad AMR exome

AF:

0.000589

Gnomad ASJ exome

AF:

0.00111

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000771

Gnomad FIN exome

AF:

0.000140

Gnomad NFE exome

AF:

0.00231

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.00243

AC:

3550

AN:

1459726

Hom.:

Cov.:

AF XY:

0.00238

AC XY:

1731

AN XY:

725892

show subpopulations

Gnomad4 AFR exome

AF:

0.000389

Gnomad4 AMR exome

AF:

0.000631

Gnomad4 ASJ exome

AF:

0.000844

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000712

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.00295

Gnomad4 OTH exome

AF:

0.00219

GnomAD4 genome

AF:

0.00130

AC:

198

AN:

152286

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00219

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00219

Hom.:

Bravo

AF:

0.00143

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00267

AC:

ExAC

AF:

0.00123

AC:

149

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

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

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Baylor Genetics

Mar 03, 2018

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.7

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

T;T

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.51

T;.

M_CAP

Benign

0.017

MetaRNN

Benign

0.0051

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.25

.;N

REVEL

Benign

0.021

Sift

Pathogenic

0.0

.;D

Sift4G

Uncertain

0.031

D;D

Vest4

0.21

MutPred

0.52

Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);

MVP

0.19

MPC

0.019

ClinPred

0.037

GERP RS

0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.055

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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