8-89914104-C-G

Variant summary

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

The NM_001126111.3(OSGIN2):ā€‹c.227C>Gā€‹(p.Ser76Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,864 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 (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

OSGIN2
NM_001126111.3 missense

Scores

11
6
2

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]

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, 0.908

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OSGIN2NM_001126111.3 linkuse as main transcriptc.227C>G p.Ser76Cys missense_variant 3/6 ENST00000451899.7 NP_001119583.1
OSGIN2NM_004337.2 linkuse as main transcriptc.95C>G p.Ser32Cys missense_variant 3/6 NP_004328.1
OSGIN2XM_011517287.4 linkuse as main transcriptc.95C>G p.Ser32Cys missense_variant 3/6 XP_011515589.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OSGIN2ENST00000451899.7 linkuse as main transcriptc.227C>G p.Ser76Cys missense_variant 3/61 NM_001126111.3 ENSP00000396445 Q9Y236-2
OSGIN2ENST00000297438.6 linkuse as main transcriptc.95C>G p.Ser32Cys missense_variant 3/61 ENSP00000297438 P1Q9Y236-1
OSGIN2ENST00000647849.1 linkuse as main transcriptc.95C>G p.Ser32Cys missense_variant 3/6 ENSP00000497119 P1Q9Y236-1
OSGIN2ENST00000520659.1 linkuse as main transcriptc.227C>G p.Ser76Cys missense_variant 3/52 ENSP00000431029

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000400
AC:
1
AN:
250286
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135326
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1458864
Hom.:
0
Cov.:
29
AF XY:
0.00000276
AC XY:
2
AN XY:
725940
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 24, 2024The c.227C>G (p.S76C) alteration is located in exon 3 (coding exon 3) of the OSGIN2 gene. This alteration results from a C to G substitution at nucleotide position 227, causing the serine (S) at amino acid position 76 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
Pathogenic
0.86
BayesDel_addAF
Pathogenic
0.29
D
BayesDel_noAF
Pathogenic
0.18
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.61
D;D;.;.
Eigen
Pathogenic
0.95
Eigen_PC
Pathogenic
0.92
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
.;D;D;D
M_CAP
Uncertain
0.091
D
MetaRNN
Pathogenic
0.91
D;D;D;D
MetaSVM
Benign
-0.51
T
MutationAssessor
Pathogenic
3.1
M;M;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.69
T
PROVEAN
Pathogenic
-4.6
.;D;D;D
REVEL
Uncertain
0.59
Sift
Pathogenic
0.0
.;D;D;D
Sift4G
Pathogenic
0.0
.;D;D;D
Polyphen
1.0
D;D;D;.
Vest4
0.89, 0.89, 0.94
MutPred
0.81
Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);.;.;
MVP
0.65
MPC
1.1
ClinPred
1.0
D
GERP RS
6.0
Varity_R
0.70
gMVP
0.83

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: rs267602037; hg19: chr8-90926332; API