rs148857745

Variant names:

• chr4-145150579-C-A
• rs148857745
• NM_001366057.1:c.1193G>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.1193G>T​(p.Gly398Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000289 in 1,612,000 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00034 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00028 (1 hom.)
• Consequence: OTUD4 NM_001366057.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 2.87
• Publications: 8 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=0.013722092).
• BS2: High AC in GnomAd4 at 52 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.1193G>T	p.Gly398Val	missense	Exon 13 of 21	NP_001352986.1	Q01804-1
	OTUD4	NM_001102653.1		c.998G>T	p.Gly333Val	missense	Exon 13 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.1193G>T	p.Gly398Val	missense	Exon 13 of 21	ENSP00000395487.2	Q01804-1
	OTUD4	ENST00000924606.1		c.1214G>T	p.Gly405Val	missense	Exon 13 of 21	ENSP00000594665.1
	OTUD4	ENST00000924608.1		c.1211G>T	p.Gly404Val	missense	Exon 13 of 21	ENSP00000594667.1

Frequencies

GnomAD3 genomes AF: 0.000342 AC: 52 AN: 151978 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000370 AC: 93 AN: 251330 AF XY: 0.000375

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00387

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000299

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000284 AC: 414 AN: 1460022 Hom.: 1 Cov.: 30 AF XY: 0.000275 AC XY: 200 AN XY: 726158

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.000358 AC: 16 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00322 AC: 84 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.000186 AC: 16 AN: 86096

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53360

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5758

European-Non Finnish (NFE) AF: 0.000229 AC: 254 AN: 1110604

Other (OTH) AF: 0.000564 AC: 34 AN: 60288

GnomAD4 genome AF: 0.000342 AC: 52 AN: 151978 Hom.: 0 Cov.: 32 AF XY: 0.000310 AC XY: 23 AN XY: 74208

African (AFR) AF: 0.0000483 AC: 2 AN: 41386

American (AMR) AF: 0.000131 AC: 2 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000519 Hom.: 0

Bravo AF: 0.000382

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000346 AC: 42

EpiCase AF: 0.000984

EpiControl AF: 0.000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
-	1	-	Variant of unknown significance (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.069	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.97	L
PhyloP100		2.9
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.092
Sift	Benign	0.12	T
Sift4G	Benign	0.080	T
Vest4		0.50
MVP		0.19
MPC		0.98
ClinPred		0.075	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.47
Mutation Taster		=24/76	disease causing

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: rs148857745; hg19: chr4-146071731;