10-72900399-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152635.3(OIT3):ā€‹c.459G>Cā€‹(p.Glu153Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000435 in 1,608,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 31)
Exomes š‘“: 0.0000041 ( 0 hom. )

Consequence

OIT3
NM_152635.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.09
Variant links:
Genes affected
OIT3 (HGNC:29953): (oncoprotein induced transcript 3) This gene was identified due to its downregulation in hepatocarcinomas. The encoded protein may be involved in liver development and function. [provided by RefSeq, Sep 2016]

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=0.12716705).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OIT3NM_152635.3 linkuse as main transcriptc.459G>C p.Glu153Asp missense_variant 3/9 ENST00000334011.10 NP_689848.1 Q8WWZ8-1
OIT3NR_130125.2 linkuse as main transcriptn.519G>C non_coding_transcript_exon_variant 3/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OIT3ENST00000334011.10 linkuse as main transcriptc.459G>C p.Glu153Asp missense_variant 3/91 NM_152635.3 ENSP00000333900.5 Q8WWZ8-1
OIT3ENST00000622652.1 linkuse as main transcriptc.459G>C p.Glu153Asp missense_variant 3/81 ENSP00000479787.1 Q8WWZ8-2

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151930
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000412
AC:
6
AN:
1456162
Hom.:
0
Cov.:
29
AF XY:
0.00000414
AC XY:
3
AN XY:
724768
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:
0.00000542
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151930
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74168
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 15, 2024The c.459G>C (p.E153D) alteration is located in exon 3 (coding exon 3) of the OIT3 gene. This alteration results from a G to C substitution at nucleotide position 459, causing the glutamic acid (E) at amino acid position 153 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
15
DANN
Uncertain
0.98
DEOGEN2
Benign
0.021
T;.
Eigen
Benign
-0.59
Eigen_PC
Benign
-0.41
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.60
T;T
M_CAP
Benign
0.0045
T
MetaRNN
Benign
0.13
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L;L
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-0.17
N;.
REVEL
Benign
0.066
Sift
Benign
0.35
T;.
Sift4G
Benign
0.47
T;T
Polyphen
0.0010
B;.
Vest4
0.23
MutPred
0.46
Gain of disorder (P = 0.2162);Gain of disorder (P = 0.2162);
MVP
0.17
MPC
0.23
ClinPred
0.11
T
GERP RS
1.2
Varity_R
0.064
gMVP
0.48

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: rs1384017038; hg19: chr10-74660157; API