rs147253069

Variant names:

• chr4-145137772-A-T
• rs147253069
• NM_001366057.1:c.3003T>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001366057.1(OTUD4):​c.3003T>A​(p.Ala1001Ala) 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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 VariationId is 211809.
• BP7: Synonymous conserved (PhyloP=1.53 with no splicing effect.
• BS2: High AC in GnomAd4 at 928 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366057.1. 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
	OTUD4	NM_001366057.1	MANE Select	c.3003T>A	p.Ala1001Ala	synonymous	Exon 21 of 21	NP_001352986.1	Q01804-1
	OTUD4	NM_001102653.1		c.2808T>A	p.Ala936Ala	synonymous	Exon 21 of 21	NP_001096123.1	Q01804-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTUD4	ENST00000447906.8	TSL:5 MANE Select	c.3003T>A	p.Ala1001Ala	synonymous	Exon 21 of 21	ENSP00000395487.2	Q01804-1
	OTUD4	ENST00000924606.1		c.3024T>A	p.Ala1008Ala	synonymous	Exon 21 of 21	ENSP00000594665.1
	OTUD4	ENST00000924608.1		c.3021T>A	p.Ala1007Ala	synonymous	Exon 21 of 21	ENSP00000594667.1

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

GnomAD2 exomes AF: 0.00630 AC: 1577 AN: 250442 AF XY: 0.00631

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 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

African (AFR) AF: 0.00134 AC: 45 AN: 33480

American (AMR) AF: 0.00499 AC: 223 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00444 AC: 116 AN: 26134

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00407 AC: 351 AN: 86258

European-Finnish (FIN) AF: 0.00943 AC: 504 AN: 53420

Middle Eastern (MID) AF: 0.00433 AC: 25 AN: 5768

European-Non Finnish (NFE) AF: 0.00881 AC: 9797 AN: 1111986

Other (OTH) AF: 0.00664 AC: 401 AN: 60396

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

African (AFR) AF: 0.00140 AC: 58 AN: 41540

American (AMR) AF: 0.00805 AC: 123 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00491 AC: 17 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00331 AC: 16 AN: 4830

European-Finnish (FIN) AF: 0.0112 AC: 119 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00849 AC: 577 AN: 67998

Other (OTH) AF: 0.00805 AC: 17 AN: 2112

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

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.1
DANN	Benign	0.63
PhyloP100		1.5
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs147253069; hg19: chr4-146058924;