Variant 8-89914127-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001126111.3(OSGIN2):c.250C>T(p.Pro84Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,232 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: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

OSGIN2
NM_001126111.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.49

Variant links:

Genes affected

OSGIN2 (HGNC:1355): (oxidative stress induced growth inhibitor family member 2) Predicted to enable growth factor activity. Predicted to be involved in negative regulation of cell growth. [provided by Alliance of Genome Resources, Apr 2022]

OSGIN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.83

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
OSGIN2	NM_001126111.3 linkuse as main transcript	c.250C>T	p.Pro84Ser	missense_variant	3/6	ENST00000451899.7	NP_001119583.1
OSGIN2	NM_004337.2 linkuse as main transcript	c.118C>T	p.Pro40Ser	missense_variant	3/6		NP_004328.1
OSGIN2	XM_011517287.4 linkuse as main transcript	c.118C>T	p.Pro40Ser	missense_variant	3/6		XP_011515589.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSGIN2	ENST00000451899.7 linkuse as main transcript	c.250C>T	p.Pro84Ser	missense_variant	3/6	1	NM_001126111.3	ENSP00000396445		Q9Y236-2
OSGIN2	ENST00000297438.6 linkuse as main transcript	c.118C>T	p.Pro40Ser	missense_variant	3/6	1		ENSP00000297438	P1	Q9Y236-1
OSGIN2	ENST00000647849.1 linkuse as main transcript	c.118C>T	p.Pro40Ser	missense_variant	3/6			ENSP00000497119	P1	Q9Y236-1
OSGIN2	ENST00000520659.1 linkuse as main transcript	c.250C>T	p.Pro84Ser	missense_variant	3/5	2		ENSP00000431029

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250768

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135584

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453232

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723674

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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 submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.250C>T (p.P84S) alteration is located in exon 3 (coding exon 3) of the OSGIN2 gene. This alteration results from a C to T substitution at nucleotide position 250, causing the proline (P) at amino acid position 84 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

Pathogenic

0.99

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.62

D;D;.;.

Eigen

Pathogenic

0.96

Eigen_PC

Pathogenic

0.93

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

.;D;D;D

M_CAP

Benign

0.083

MetaRNN

Pathogenic

0.83

D;D;D;D

MetaSVM

Benign

-0.60

MutationAssessor

Pathogenic

3.1

M;M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-7.3

.;D;D;D

REVEL

Uncertain

0.50

Sift

Uncertain

0.012

.;D;D;D

Sift4G

Uncertain

0.0090

.;D;D;D

Polyphen

1.0

D;D;D;.

Vest4

0.96, 0.97

MutPred

0.70

Gain of phosphorylation at P40 (P = 0.0598);Gain of phosphorylation at P40 (P = 0.0598);.;.;

MVP

0.53

MPC

1.1

ClinPred

0.99

GERP RS

6.0

Varity_R

0.65

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over