10-23439765-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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. 11/19 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

Scores

2
3
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.143
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.0981859).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OTUD1NM_001145373.3 linkc.308C>T p.Pro103Leu missense_variant Exon 1 of 1 ENST00000376495.5 NP_001138845.1 Q5VV17

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OTUD1ENST00000376495.5 linkc.308C>T p.Pro103Leu missense_variant Exon 1 of 1 6 NM_001145373.3 ENSP00000365678.3 Q5VV17
ENSG00000287124ENST00000702412.1 linkn.88+720C>T intron_variant Intron 1 of 2

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
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000342
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
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

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs966867570; hg19: chr10-23728694; API