10-23439597-A-T

Variant names:

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

Variant summary

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

The NM_001145373.3(OTUD1):​c.140A>T​(p.Glu47Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000165 in 1,213,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E47A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: OTUD1 NM_001145373.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48
• Publications: 0 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: 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=0.19162282).

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>T	p.Glu47Val	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>T	p.Glu47Val	missense	Exon 1 of 1	ENSP00000365678.3	Q5VV17
	ENSG00000287124	ENST00000702412.1		n.88+552A>T		intron	N/A
	ENSG00000287124	ENST00000848567.1		n.109+1063A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000165 AC: 2 AN: 1213320 Hom.: 0 Cov.: 30 AF XY: 0.00000167 AC XY: 1 AN XY: 597416

African (AFR) AF: 0.00 AC: 0 AN: 24002

American (AMR) AF: 0.00 AC: 0 AN: 19618

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18992

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

South Asian (SAS) AF: 0.0000331 AC: 2 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: 0.00 AC: 0 AN: 985992

Other (OTH) AF: 0.00 AC: 0 AN: 48176

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.40	T
M_CAP	Pathogenic	0.69	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.5
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.13
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.42	T
Polyphen		0.90	P
Vest4		0.15
MutPred		0.12		Loss of glycosylation at P48 (P = 0.1119)
MVP		0.23
ClinPred		0.49	T
GERP RS		2.2
Varity_R		0.17
gMVP		0.45
Mutation Taster		=94/6	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: rs753468771; hg19: chr10-23728526;