Variant 14-94038966-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_023112.4(OTUB2):c.103C>G(p.Leu35Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,806 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 1 hom. )

Consequence

OTUB2
NM_023112.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.59

Variant links:

Genes affected

OTUB2 (HGNC:20351): (OTU deubiquitinase, ubiquitin aldehyde binding 2) This gene encodes one of several deubiquitylating enzymes. Ubiquitin modification of proteins is needed for their stability and function; to reverse the process, deubiquityling enzymes remove ubiquitin. This protein contains an OTU domain and binds Ubal (ubiquitin aldehyde); an active cysteine protease site is present in the OTU domain. [provided by RefSeq, Aug 2011]

OTUB2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.86

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTUB2	NM_023112.4 link	c.103C>G	p.Leu35Val	missense_variant	3/6	ENST00000203664.10	NP_075601.1	Q96DC9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTUB2	ENST00000203664.10 link	c.103C>G	p.Leu35Val	missense_variant	3/6	1	NM_023112.4	ENSP00000203664.5		Q96DC9-1
OTUB2	ENST00000553723.1 link	c.103C>G	p.Leu35Val	missense_variant	3/3	1		ENSP00000451283.1		Q96DC9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000278

AC:

AN:

251492

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135920

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:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461806

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727214

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:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2023

The c.103C>G (p.L35V) alteration is located in exon 3 (coding exon 3) of the OTUB2 gene. This alteration results from a C to G substitution at nucleotide position 103, causing the leucine (L) at amino acid position 35 to be replaced by a valine (V). 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

Benign

0.33

BayesDel_addAF

Uncertain

0.095

BayesDel_noAF

Pathogenic

0.19

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.52

D;.

Eigen

Pathogenic

0.68

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.97

M_CAP

Benign

0.051

MetaRNN

Pathogenic

0.86

D;D

MetaSVM

Uncertain

0.15

MutationAssessor

Uncertain

2.6

M;M

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.7

D;D

REVEL

Pathogenic

0.67

Sift

Uncertain

0.0020

D;D

Sift4G

Benign

0.061

T;T

Polyphen

0.97

D;.

Vest4

0.72

MutPred

0.73

Gain of catalytic residue at R38 (P = 0.0516);Gain of catalytic residue at R38 (P = 0.0516);

MVP

0.71

MPC

0.52

ClinPred

0.76

GERP RS

5.6

Varity_R

0.86

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.36

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.36

Position offset: 1

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