10-72906664-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_152635.3(OIT3):​c.613C>T​(p.Arg205Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000347 in 1,612,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

OIT3
NM_152635.3 missense

Scores

11
6
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.82
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.868

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OIT3NM_152635.3 linkuse as main transcriptc.613C>T p.Arg205Cys missense_variant 4/9 ENST00000334011.10 NP_689848.1 Q8WWZ8-1
OIT3NR_130125.2 linkuse as main transcriptn.673C>T non_coding_transcript_exon_variant 4/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OIT3ENST00000334011.10 linkuse as main transcriptc.613C>T p.Arg205Cys missense_variant 4/91 NM_152635.3 ENSP00000333900.5 Q8WWZ8-1
OIT3ENST00000622652.1 linkuse as main transcriptc.613C>T p.Arg205Cys missense_variant 4/81 ENSP00000479787.1 Q8WWZ8-2

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152086
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000562
AC:
14
AN:
249022
Hom.:
0
AF XY:
0.0000446
AC XY:
6
AN XY:
134556
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000804
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000330
Gnomad FIN exome
AF:
0.0000466
Gnomad NFE exome
AF:
0.0000355
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000349
AC:
51
AN:
1459972
Hom.:
0
Cov.:
31
AF XY:
0.0000317
AC XY:
23
AN XY:
726260
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000883
Gnomad4 EAS exome
AF:
0.000126
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000144
Gnomad4 OTH exome
AF:
0.0000829
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152086
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000143
Hom.:
0
Bravo
AF:
0.0000302
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000577
AC:
7

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 GeneticsNov 29, 2023The c.613C>T (p.R205C) alteration is located in exon 4 (coding exon 4) of the OIT3 gene. This alteration results from a C to T substitution at nucleotide position 613, causing the arginine (R) at amino acid position 205 to be replaced by a cysteine (C). 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
0.19
BayesDel_addAF
Pathogenic
0.44
D
BayesDel_noAF
Pathogenic
0.50
CADD
Pathogenic
33
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.75
D;.
Eigen
Pathogenic
0.88
Eigen_PC
Pathogenic
0.85
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.99
D;D
M_CAP
Uncertain
0.24
D
MetaRNN
Pathogenic
0.87
D;D
MetaSVM
Pathogenic
1.0
D
MutationAssessor
Uncertain
2.7
M;M
PrimateAI
Uncertain
0.58
T
PROVEAN
Uncertain
-2.6
D;.
REVEL
Pathogenic
0.81
Sift
Pathogenic
0.0
D;.
Sift4G
Uncertain
0.012
D;T
Polyphen
1.0
D;.
Vest4
0.95
MVP
0.76
MPC
1.1
ClinPred
0.66
D
GERP RS
5.8
Varity_R
0.43
gMVP
0.78

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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: rs139396966; hg19: chr10-74666422; API