rs4561948

Variant names:

• chr4-145137782-G-A
• rs4561948
• NM_001366057.1:c.2993C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-145137782-G-A
• chr4-145137782-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001366057.1(OTUD4):​c.2993C>T​(p.Pro998Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OTUD4 NM_001366057.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.97

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.071056366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTUD4	NM_001366057.1	c.2993C>T	p.Pro998Leu	missense_variant	Exon 21 of 21	ENST00000447906.8	NP_001352986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTUD4	ENST00000447906.8	c.2993C>T	p.Pro998Leu	missense_variant	Exon 21 of 21	5	NM_001366057.1	ENSP00000395487.2
OTUD4	ENST00000454497.6	c.2798C>T	p.Pro933Leu	missense_variant	Exon 21 of 21	2		ENSP00000409279.2
OTUD4	ENST00000455611.6	n.2028+2169C>T		intron_variant	Intron 20 of 21	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	.;T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.033
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.071	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	.;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.78	N;N
REVEL	Benign	0.031
Sift	Benign	0.041	D;D
Sift4G	Benign	0.071	T;T
Vest4		0.064
MVP		0.15
MPC		0.31
ClinPred		0.35	T
GERP RS		5.3
Varity_R		0.066
gMVP		0.088

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: rs4561948; hg19: chr4-146058934;