10-23439597-A-C

Variant names:

• chr10-23439597-A-C
• rs753468771
• NM_001145373.3:c.140A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001145373.3(OTUD1):​c.140A>C​(p.Glu47Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000185 in 1,361,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: OTUD1 NM_001145373.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.48
• Publications: 1 publications found

Genes affected

OTUD1 (HGNC:27346): (OTU deubiquitinase 1) Deubiquitinating enzymes (DUBs; see MIM 603478) are proteases that specifically cleave ubiquitin (MIM 191339) linkages, negating the action of ubiquitin ligases. DUBA7 belongs to a DUB subfamily characterized by an ovarian tumor (OTU) domain.[supplied by OMIM, May 2008]

ENSG00000287124 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003927499).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145373.3. 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
	OTUD1	NM_001145373.3	MANE Select	c.140A>C	p.Glu47Ala	missense	Exon 1 of 1	NP_001138845.1	Q5VV17

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTUD1	ENST00000376495.5	TSL:6 MANE Select	c.140A>C	p.Glu47Ala	missense	Exon 1 of 1	ENSP00000365678.3	Q5VV17
	ENSG00000287124	ENST00000702412.1		n.88+552A>C		intron	N/A
	ENSG00000287124	ENST00000848567.1		n.109+1063A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000128 AC: 19 AN: 147986 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00146

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000180

Gnomad OTH AF: 0.000987

GnomAD2 exomes AF: 0.000206 AC: 12 AN: 58344 AF XY: 0.000261

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000929

Gnomad ASJ exome AF: 0.000937

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000233

Gnomad OTH exome AF: 0.000575

GnomAD4 exome AF: 0.000192 AC: 233 AN: 1213318 Hom.: 0 Cov.: 30 AF XY: 0.000189 AC XY: 113 AN XY: 597416

African (AFR) AF: 0.0000417 AC: 1 AN: 24002

American (AMR) AF: 0.000102 AC: 2 AN: 19618

Ashkenazi Jewish (ASJ) AF: 0.00174 AC: 33 AN: 18992

East Asian (EAS) AF: 0.00 AC: 0 AN: 23952

South Asian (SAS) AF: 0.00 AC: 0 AN: 60336

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28874

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3378

European-Non Finnish (NFE) AF: 0.000195 AC: 192 AN: 985990

Other (OTH) AF: 0.000104 AC: 5 AN: 48176

GnomAD4 genome AF: 0.000128 AC: 19 AN: 147986 Hom.: 0 Cov.: 32 AF XY: 0.000125 AC XY: 9 AN XY: 72192

African (AFR) AF: 0.00 AC: 0 AN: 40252

American (AMR) AF: 0.00 AC: 0 AN: 14968

Ashkenazi Jewish (ASJ) AF: 0.00146 AC: 5 AN: 3414

East Asian (EAS) AF: 0.00 AC: 0 AN: 4950

South Asian (SAS) AF: 0.00 AC: 0 AN: 4706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9796

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 300

European-Non Finnish (NFE) AF: 0.000180 AC: 12 AN: 66680

Other (OTH) AF: 0.000987 AC: 2 AN: 2026

Alfa AF: 0.0000612 Hom.: 0

Bravo AF: 0.000170

ExAC AF: 0.000350 AC: 4

ClinVar

ClinVar submissions

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	0.078
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.0077	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.5
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.035
Sift	Benign	0.28	T
Sift4G	Benign	0.88	T
Polyphen		0.37	B
Vest4		0.092
MutPred		0.10		Gain of glycosylation at P46 (P = 0.1441)
MVP		0.19
ClinPred		0.087	T
GERP RS		2.2
Varity_R		0.095
gMVP		0.35
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs753468771; hg19: chr10-23728526;