rs149518451

Variant names:

• chr4-145138037-G-A
• rs149518451
• NM_001366057.1:c.2738C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001366057.1(OTUD4):​c.2738C>T​(p.Pro913Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000929 in 1,614,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000090 (0 hom.)
• Consequence: OTUD4 NM_001366057.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0380
• Publications: 0 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.026110023).
• BS2: High AC in GnomAd4 at 19 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.2738C>T	p.Pro913Leu	missense	Exon 21 of 21	NP_001352986.1	Q01804-1
	OTUD4	NM_001102653.1		c.2543C>T	p.Pro848Leu	missense	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.2738C>T	p.Pro913Leu	missense	Exon 21 of 21	ENSP00000395487.2	Q01804-1
	OTUD4	ENST00000924606.1		c.2759C>T	p.Pro920Leu	missense	Exon 21 of 21	ENSP00000594665.1
	OTUD4	ENST00000924608.1		c.2756C>T	p.Pro919Leu	missense	Exon 21 of 21	ENSP00000594667.1

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152196 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000107 AC: 27 AN: 251230 AF XY: 0.000133

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000896 AC: 131 AN: 1461868 Hom.: 0 Cov.: 33 AF XY: 0.0000880 AC XY: 64 AN XY: 727232

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.000179 AC: 8 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.0000971 AC: 108 AN: 1112008

Other (OTH) AF: 0.0000994 AC: 6 AN: 60392

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152314 Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74480

African (AFR) AF: 0.0000481 AC: 2 AN: 41572

American (AMR) AF: 0.000196 AC: 3 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000140 Hom.: 0

Bravo AF: 0.000117

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000148 AC: 18

EpiCase AF: 0.000109

EpiControl AF: 0.000533

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.85
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.62
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.038
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.045
Sift	Benign	0.33	T
Sift4G	Benign	0.68	T
Vest4		0.089
MVP		0.14
MPC		0.28
ClinPred		0.028	T
GERP RS		0.22
Varity_R		0.026
gMVP		0.11
Mutation Taster		=91/9	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: rs149518451; hg19: chr4-146059189;