Genetic Variant OTUD1:p.Leu104Leu (chr10-23439767-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_001145373.3(OTUD1):c.310C>T(p.Leu104Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000601 in 1,157,304 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00066 ( 2 hom. )

Consequence

OTUD1
NM_001145373.3 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.896

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 10-23439767-C-T is Benign according to our data. Variant chr10-23439767-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3043264.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.896 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTUD1	NM_001145373.3 link	c.310C>T	p.Leu104Leu	synonymous_variant	Exon 1 of 1	ENST00000376495.5	NP_001138845.1	Q5VV17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTUD1	ENST00000376495.5 link	c.310C>T	p.Leu104Leu	synonymous_variant	Exon 1 of 1	6	NM_001145373.3	ENSP00000365678.3		Q5VV17
ENSG00000287124	ENST00000702412.1 link	n.88+722C>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.000182

AC:

AN:

148556

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000146

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000315

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000150

AC:

AN:

13366

Hom.:

AF XY:

0.000241

AC XY:

AN XY:

8304

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000363

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000663

AC:

669

AN:

1008748

Hom.:

Cov.:

AF XY:

0.000662

AC XY:

321

AN XY:

484974

show subpopulations

Gnomad4 AFR exome

AF:

0.0000513

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000940

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000745

Gnomad4 OTH exome

AF:

0.000376

GnomAD4 genome

AF:

0.000182

AC:

AN:

148556

Hom.:

Cov.:

AF XY:

0.000180

AC XY:

AN XY:

72364

show subpopulations

Gnomad4 AFR

AF:

0.000146

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000315

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

OTUD1-related disorder

Benign:1

Jun 27, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.98

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