Variant chr1-19882583-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015207.2(OTUD3):c.70C>T(p.Arg24Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 1,406,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

OTUD3
NM_015207.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.46

Variant links:

Genes affected

OTUD3 (HGNC:29038): (OTU deubiquitinase 3) Enables thiol-dependent deubiquitinase. Acts upstream of or within negative regulation of protein kinase B signaling; protein deubiquitination; and protein stabilization. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

OTUD3 links:

LOC105376823 (HGNC:):

LOC105376823 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39527237).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTUD3	NM_015207.2 linkuse as main transcript	c.70C>T	p.Arg24Trp	missense_variant	1/8	ENST00000375120.4
LOC105376823	XR_947028.3 linkuse as main transcript	n.41+6541G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTUD3	ENST00000375120.4 linkuse as main transcript	c.70C>T	p.Arg24Trp	missense_variant	1/8	1	NM_015207.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.0000128

AC:

AN:

1254156

Hom.:

Cov.:

AF XY:

0.0000130

AC XY:

AN XY:

614430

show subpopulations

Gnomad4 AFR exome

AF:

0.0000398

Gnomad4 AMR exome

AF:

0.000123

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:

0.00000884

Gnomad4 OTH exome

AF:

0.0000773

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000907

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

Apr 04, 2023

The c.70C>T (p.R24W) alteration is located in exon 1 (coding exon 1) of the OTUD3 gene. This alteration results from a C to T substitution at nucleotide position 70, causing the arginine (R) at amino acid position 24 to be replaced by a tryptophan (W). 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

Pathogenic

0.85

BayesDel_addAF

Uncertain

0.045

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.93

M_CAP

Pathogenic

0.91

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.74

MutationAssessor

Benign

2.0

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.97

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.24

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.25

MutPred

0.41

Loss of solvent accessibility (P = 0.1077);

MVP

0.68

MPC

0.99

ClinPred

1.0

GERP RS

4.6

Varity_R

0.69

gMVP

0.54

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