NM_001366057.1:c.3001G>C

Variant names:

• chr4-145137774-C-G
• rs1256721513
• NM_001366057.1:c.3001G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001366057.1(OTUD4):​c.3001G>C​(p.Ala1001Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A1001A) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: OTUD4 NM_001366057.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0600
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10789606).

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.3001G>C	p.Ala1001Pro	missense	Exon 21 of 21	NP_001352986.1	Q01804-1
	OTUD4	NM_001102653.1		c.2806G>C	p.Ala936Pro	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.3001G>C	p.Ala1001Pro	missense	Exon 21 of 21	ENSP00000395487.2	Q01804-1
	OTUD4	ENST00000924606.1		c.3022G>C	p.Ala1008Pro	missense	Exon 21 of 21	ENSP00000594665.1
	OTUD4	ENST00000924608.1		c.3019G>C	p.Ala1007Pro	missense	Exon 21 of 21	ENSP00000594667.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152108 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152108 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74298

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.0000655 AC: 1 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	0.097
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.062	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		-0.060
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.085
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.033	D
Vest4		0.11
MVP		0.18
MPC		0.93
ClinPred		0.46	T
GERP RS		1.9
Varity_R		0.18
gMVP		0.16
Mutation Taster		=80/20	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: rs1256721513; hg19: chr4-146058926;