10-72893802-C-T

Position:

• chr10-72893802-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152635.3(OIT3):​c.4C>T​(p.Pro2Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: OIT3 NM_152635.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.379

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]

OIT3 (HGNC:):

ACMG classification

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=0.08364022).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OIT3	NM_152635.3	c.4C>T	p.Pro2Ser	missense_variant	1/9	ENST00000334011.10	NP_689848.1
OIT3	NR_130125.2	n.64C>T		non_coding_transcript_exon_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OIT3	ENST00000334011.10	c.4C>T	p.Pro2Ser	missense_variant	1/9	1	NM_152635.3	ENSP00000333900.5
OIT3	ENST00000622652.1	c.4C>T	p.Pro2Ser	missense_variant	1/8	1		ENSP00000479787.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2022

The c.4C>T (p.P2S) alteration is located in exon 1 (coding exon 1) of the OIT3 gene. This alteration results from a C to T substitution at nucleotide position 4, causing the proline (P) at amino acid position 2 to be replaced by a serine (S). 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	0.067
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.33
DANN	Benign	0.81
DEOGEN2	Benign	0.020	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.58	T;T
M_CAP	Uncertain	0.094	D
MetaRNN	Benign	0.084	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.31	N;.
REVEL	Benign	0.098
Sift	Benign	0.12	T;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.0	B;.
Vest4		0.049
MutPred		0.32		Loss of glycosylation at P3 (P = 0.0549);Loss of glycosylation at P3 (P = 0.0549);
MVP		0.19
MPC		0.26
ClinPred		0.035	T
GERP RS		-2.2
Varity_R		0.027
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-74653560;