Variant NM_016023.5:c.19G>T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate

The NM_016023.5(OTUD6B):c.19G>T(p.Glu7*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,452,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

OTUD6B
NM_016023.5 stop_gained

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 3.28

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 made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.978 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 8-91070403-G-T is Pathogenic according to our data. Variant chr8-91070403-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 1452195.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTUD6B	NM_016023.5 link	c.19G>T	p.Glu7*	stop_gained	Exon 1 of 7	ENST00000404789.8	NP_057107.4	Q8N6M0-1A0A087X0W9
OTUD6B	NM_001416022.1 link	c.19G>T	p.Glu7*	stop_gained	Exon 1 of 6		NP_001402951.1
OTUD6B	XM_047421864.1 link	c.19G>T	p.Glu7*	stop_gained	Exon 1 of 4		XP_047277820.1
OTUD6B	NM_001286745.3 link	c.-425G>T		5_prime_UTR_variant	Exon 1 of 8		NP_001273674.1	Q8N6M0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTUD6B	ENST00000404789.8 link	c.19G>T	p.Glu7*	stop_gained	Exon 1 of 7	1	NM_016023.5	ENSP00000384190.4		Q8N6M0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000130

AC:

AN:

231238

Hom.:

AF XY:

0.00000802

AC XY:

AN XY:

124626

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000624

Gnomad ASJ exome

AF:

0.000104

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1452102

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000700

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.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Pathogenic:1

Nov 27, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with OTUD6B-related conditions. For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Glu37*) in the OTUD6B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in OTUD6B are known to be pathogenic (PMID: 28343629). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.63

BayesDel_noAF

Pathogenic

0.49

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.89

Vest4

0.14

GERP RS

5.7

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

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