chr10-23439765-C-T

Variant names:

• chr10-23439765-C-T
• rs966867570
• NM_001145373.3:c.308C>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.308C>T​(p.Pro103Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000298 in 1,008,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. P103R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: OTUD1 NM_001145373.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.143
• 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=0.0981859).

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.308C>T	p.Pro103Leu	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.308C>T	p.Pro103Leu	missense	Exon 1 of 1	ENSP00000365678.3	Q5VV17
	ENSG00000287124	ENST00000702412.1		n.88+720C>T		intron	N/A
	ENSG00000287124	ENST00000848567.1		n.109+1231C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000298 AC: 3 AN: 1008242 Hom.: 0 Cov.: 30 AF XY: 0.00000206 AC XY: 1 AN XY: 484686

African (AFR) AF: 0.00 AC: 0 AN: 19482

American (AMR) AF: 0.00 AC: 0 AN: 7054

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10578

East Asian (EAS) AF: 0.00 AC: 0 AN: 14712

South Asian (SAS) AF: 0.00 AC: 0 AN: 25006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15236

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2514

European-Non Finnish (NFE) AF: 0.00000342 AC: 3 AN: 876376

Other (OTH) AF: 0.00 AC: 0 AN: 37284

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0062	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.60	T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.14
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.026
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.12	B
Vest4		0.12
MutPred		0.33		Loss of glycosylation at P103 (P = 0.0042)
MVP		0.20
ClinPred		0.49	T
GERP RS		2.2
Varity_R		0.13
gMVP		0.30
Mutation Taster		=84/16	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: rs966867570; hg19: chr10-23728694;