Variant chr10-23439597-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001145373.3(OTUD1):c.140A>C(p.Glu47Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000185 in 1,361,304 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

OTUD1
NM_001145373.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.48

Variant links:

Genes affected

OTUD1 (HGNC:27346): (OTU deubiquitinase 1) Deubiquitinating enzymes (DUBs; see MIM 603478) are proteases that specifically cleave ubiquitin (MIM 191339) linkages, negating the action of ubiquitin ligases. DUBA7 belongs to a DUB subfamily characterized by an ovarian tumor (OTU) domain.[supplied by OMIM, May 2008]

OTUD1 links:

ENSG00000287124 (HGNC:):

ENSG00000287124 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.003927499).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTUD1	NM_001145373.3 linkuse as main transcript	c.140A>C	p.Glu47Ala	missense_variant	1/1	ENST00000376495.5	NP_001138845.1	Q5VV17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTUD1	ENST00000376495.5 linkuse as main transcript	c.140A>C	p.Glu47Ala	missense_variant	1/1	6	NM_001145373.3	ENSP00000365678.3		Q5VV17
ENSG00000287124	ENST00000702412.1 linkuse as main transcript	n.88+552A>C		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.000128

AC:

AN:

147986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00146

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000180

Gnomad OTH

AF:

0.000987

GnomAD3 exomes

AF:

0.000206

AC:

AN:

58344

Hom.:

AF XY:

0.000261

AC XY:

AN XY:

34492

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000929

Gnomad ASJ exome

AF:

0.000937

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000233

Gnomad OTH exome

AF:

0.000575

GnomAD4 exome

AF:

0.000192

AC:

233

AN:

1213318

Hom.:

Cov.:

AF XY:

0.000189

AC XY:

113

AN XY:

597416

show subpopulations

Gnomad4 AFR exome

AF:

0.0000417

Gnomad4 AMR exome

AF:

0.000102

Gnomad4 ASJ exome

AF:

0.00174

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000195

Gnomad4 OTH exome

AF:

0.000104

GnomAD4 genome

AF:

0.000128

AC:

AN:

147986

Hom.:

Cov.:

AF XY:

0.000125

AC XY:

AN XY:

72192

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00146

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000180

Gnomad4 OTH

AF:

0.000987

Alfa

AF:

0.0000612

Hom.:

Bravo

AF:

0.000170

ExAC

AF:

0.000350

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

Nov 30, 2022

The c.140A>C (p.E47A) alteration is located in exon 1 (coding exon 1) of the OTUD1 gene. This alteration results from a A to C substitution at nucleotide position 140, causing the glutamic acid (E) at amino acid position 47 to be replaced by an alanine (A). 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

0.078

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0077

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0039

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.35

REVEL

Benign

0.035

Sift

Benign

0.28

Sift4G

Benign

0.88

Polyphen

0.37

Vest4

0.092

MutPred

0.10

Gain of glycosylation at P46 (P = 0.1441);

MVP

0.19

ClinPred

0.087

GERP RS

2.2

Varity_R

0.095

gMVP

0.35

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