Genetic Variant OTUD1:p.Pro38Ser (chr10-23439569-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001145373.3(OTUD1):c.112C>T(p.Pro38Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,372,240 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 1 hom. )

Consequence

OTUD1
NM_001145373.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.955

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0070511997).

BP6

Variant 10-23439569-C-T is Benign according to our data. Variant chr10-23439569-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3046356.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145373.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTUD1	NM_001145373.3	MANE Select	c.112C>T	p.Pro38Ser	missense	Exon 1 of 1	NP_001138845.1	Q5VV17

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OTUD1	ENST00000376495.5	TSL:6 MANE Select	c.112C>T	p.Pro38Ser	missense	Exon 1 of 1	ENSP00000365678.3	Q5VV17
ENSG00000287124	ENST00000702412.1		n.88+524C>T		intron	N/A
ENSG00000287124	ENST00000848567.1		n.109+1035C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000730

AC:

AN:

150668

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000196

Gnomad SAS

AF:

0.00208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000454

AC:

AN:

57320

AF XY:

0.000592

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000931

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000480

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000138

AC:

168

AN:

1221464

Hom.:

Cov.:

AF XY:

0.000191

AC XY:

115

AN XY:

601388

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24280

American (AMR)

AF:

0.0000508

AC:

AN:

19704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19270

East Asian (EAS)

AF:

0.00

AC:

AN:

24866

South Asian (SAS)

AF:

0.00262

AC:

158

AN:

60228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29294

Middle Eastern (MID)

AF:

0.000293

AC:

AN:

3410

European-Non Finnish (NFE)

AF:

0.00000303

AC:

AN:

991490

Other (OTH)

AF:

0.000102

AC:

AN:

48922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.534

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000730

AC:

AN:

150776

Hom.:

Cov.:

AF XY:

0.0000814

AC XY:

AN XY:

73680

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41368

American (AMR)

AF:

0.00

AC:

AN:

15176

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.000196

AC:

AN:

5090

South Asian (SAS)

AF:

0.00208

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10088

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67506

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.000858

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

OTUD1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.012

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.44

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.0071

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

0.95

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

0.20

REVEL

Benign

0.020

Sift

Benign

0.42

Sift4G

Benign

0.21

Polyphen

0.0010

Vest4

0.052

MutPred

0.20

Loss of catalytic residue at P38 (P = 0.0059)

MVP

0.055

ClinPred

0.024

GERP RS

-0.39

PromoterAI

-0.022

Neutral

(source)

Varity_R

0.031

gMVP

0.25

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over