rs147253069

chr4-145137772-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001366057.1(OTUD4):c.3003T>A(p.Ala1001=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00768 in 1,614,062 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0061 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0078 (58 hom.)
• Consequence: OTUD4 NM_001366057.1 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: 1.53

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 4-145137772-A-T is Benign according to our data. Variant chr4-145137772-A-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 211809.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Likely_benign=1, Uncertain_significance=1}.
• BP7: Synonymous conserved (PhyloP=1.53 with no splicing effect.
• BS2: High AC in GnomAd at 930 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTUD4	NM_001366057.1	c.3003T>A	p.Ala1001=	synonymous_variant	21/21	ENST00000447906.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTUD4	ENST00000447906.8	c.3003T>A	p.Ala1001=	synonymous_variant	21/21	5	NM_001366057.1	P1
OTUD4	ENST00000454497.6	c.2808T>A	p.Ala936=	synonymous_variant	21/21	2
OTUD4	ENST00000455611.6	n.2028+2179T>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00612 AC: 930 AN: 152078 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00806

Gnomad ASJ AF: 0.00491

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.0112

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00848

Gnomad OTH AF: 0.00813

GnomAD3 exomes AF: 0.00630 AC: 1577 AN: 250442 Hom.: 9 AF XY: 0.00631 AC XY: 856 AN XY: 135620

Gnomad AFR exome AF: 0.00133

Gnomad AMR exome AF: 0.00445

Gnomad ASJ exome AF: 0.00397

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00392

Gnomad FIN exome AF: 0.00924

Gnomad NFE exome AF: 0.00885

Gnomad OTH exome AF: 0.00640

GnomAD4 exome AF: 0.00784 AC: 11464 AN: 1461866 Hom.: 58 Cov.: 33 AF XY: 0.00781 AC XY: 5683 AN XY: 727234

Gnomad4 AFR exome AF: 0.00134

Gnomad4 AMR exome AF: 0.00499

Gnomad4 ASJ exome AF: 0.00444

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00407

Gnomad4 FIN exome AF: 0.00943

Gnomad4 NFE exome AF: 0.00881

Gnomad4 OTH exome AF: 0.00664

GnomAD4 genome AF: 0.00610 AC: 928 AN: 152196 Hom.: 5 Cov.: 32 AF XY: 0.00606 AC XY: 451 AN XY: 74420

Gnomad4 AFR AF: 0.00140

Gnomad4 AMR AF: 0.00805

Gnomad4 ASJ AF: 0.00491

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00331

Gnomad4 FIN AF: 0.0112

Gnomad4 NFE AF: 0.00849

Gnomad4 OTH AF: 0.00805

Alfa AF: 0.00717 Hom.: 1

Bravo AF: 0.00563

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00894

EpiControl AF: 0.00806

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2023	OTUD4: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jul 26, 2018	- -

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jun 27, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	6.1
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

Other links and lift over

dbSNP: rs147253069; hg19: chr4-146058924;