Variant X-48925907-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001136157.2(OTUD5):c.1203C>G(p.Ser401=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00269 in 1,209,743 control chromosomes in the GnomAD database, including 3 homozygotes. There are 1,010 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., 50 hem., cov: 23)

Exomes 𝑓: 0.0028 ( 2 hom. 960 hem. )

Consequence

OTUD5
NM_001136157.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.589

Variant links:

Genes affected

OTUD5 (HGNC:25402): (OTU deubiquitinase 5) This gene encodes a member of the OTU (ovarian tumor) domain-containing cysteine protease superfamily. The OTU domain confers deubiquitinase activity and the encoded protein has been shown to suppress the type I interferon-dependent innate immune response by cleaving the polyubiquitin chain from an essential type I interferon adaptor protein. Cleavage results in disassociation of the adaptor protein from a downstream signaling complex and disruption of the type I interferon signaling cascade. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Oct 2008]

OTUD5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant X-48925907-G-C is Benign according to our data. Variant chrX-48925907-G-C is described in ClinVar as [Benign]. Clinvar id is 774751.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.589 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 50 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTUD5	NM_001136157.2 linkuse as main transcript	c.1203C>G	p.Ser401=	synonymous_variant	6/9	ENST00000376488.8	NP_001129629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTUD5	ENST00000376488.8 linkuse as main transcript	c.1203C>G	p.Ser401=	synonymous_variant	6/9	1	NM_001136157.2	ENSP00000365671	P4	Q96G74-5

Frequencies

GnomAD3 genomes

AF:

0.00191

AC:

214

AN:

111923

Hom.:

Cov.:

AF XY:

0.00150

AC XY:

AN XY:

34111

show subpopulations

Gnomad AFR

AF:

0.000260

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000571

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00184

Gnomad FIN

AF:

0.000490

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00358

Gnomad OTH

AF:

0.00133

GnomAD3 exomes

AF:

0.00229

AC:

418

AN:

182237

Hom.:

AF XY:

0.00235

AC XY:

157

AN XY:

66795

show subpopulations

Gnomad AFR exome

AF:

0.000153

Gnomad AMR exome

AF:

0.00186

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00338

Gnomad FIN exome

AF:

0.000759

Gnomad NFE exome

AF:

0.00341

Gnomad OTH exome

AF:

0.00266

GnomAD4 exome

AF:

0.00277

AC:

3039

AN:

1097767

Hom.:

Cov.:

AF XY:

0.00264

AC XY:

960

AN XY:

363143

show subpopulations

Gnomad4 AFR exome

AF:

0.000493

Gnomad4 AMR exome

AF:

0.00202

Gnomad4 ASJ exome

AF:

0.000206

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00290

Gnomad4 FIN exome

AF:

0.000815

Gnomad4 NFE exome

AF:

0.00315

Gnomad4 OTH exome

AF:

0.00230

GnomAD4 genome

AF:

0.00190

AC:

213

AN:

111976

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

AN XY:

34174

show subpopulations

Gnomad4 AFR

AF:

0.000259

Gnomad4 AMR

AF:

0.000570

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00185

Gnomad4 FIN

AF:

0.000490

Gnomad4 NFE

AF:

0.00358

Gnomad4 OTH

AF:

0.000657

Alfa

AF:

0.00189

Hom.:

Bravo

AF:

0.00184

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

7.3

DANN

Benign

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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