Genetic Variant OTUD4:p.Asn1010Asn (chr4-145137745-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

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

The NM_001366057.1(OTUD4):c.3030C>T(p.Asn1010Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,613,856 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00081 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 4 hom. )

Consequence

OTUD4
NM_001366057.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.03

Variant links:

Genes affected

OTUD4 (HGNC:24949): (OTU deubiquitinase 4) Alternatively spliced transcript variants have been found for this gene. The smaller protein isoform encoded by the shorter transcript variant is found only in HIV-1 infected cells. [provided by RefSeq, Jul 2010]

OTUD4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 4-145137745-G-A is Benign according to our data. Variant chr4-145137745-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2655109.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.03 with no splicing effect.

BS2

High AC in GnomAd4 at 123 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTUD4	NM_001366057.1 link	c.3030C>T	p.Asn1010Asn	synonymous_variant	Exon 21 of 21	ENST00000447906.8	NP_001352986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OTUD4	ENST00000447906.8 link	c.3030C>T	p.Asn1010Asn	synonymous_variant	Exon 21 of 21	5	NM_001366057.1	ENSP00000395487.2	Q01804-1
OTUD4	ENST00000454497.6 link	c.2835C>T	p.Asn945Asn	synonymous_variant	Exon 21 of 21	2		ENSP00000409279.2	Q01804-3
OTUD4	ENST00000455611.6 link	n.2028+2206C>T		intron_variant	Intron 20 of 21	5

Frequencies

GnomAD3 genomes

AF:

0.000809

AC:

123

AN:

151992

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

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:

0.0000946

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000718

AC:

180

AN:

250634

Hom.:

AF XY:

0.000715

AC XY:

AN XY:

135668

show subpopulations

Gnomad AFR exome

AF:

0.000189

Gnomad AMR exome

AF:

0.000173

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:

0.00148

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.00142

AC:

2078

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

1002

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00178

Gnomad4 OTH exome

AF:

0.00139

GnomAD4 genome

AF:

0.000809

AC:

123

AN:

151992

Hom.:

Cov.:

AF XY:

0.000714

AC XY:

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.000218

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000946

Gnomad4 NFE

AF:

0.00162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00114

Hom.:

Bravo

AF:

0.000771

EpiCase

AF:

0.00169

EpiControl

AF:

0.00154

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Sep 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

OTUD4: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

4.7

DANN

Benign

0.63

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