Genetic Variant OSGIN1:p.Ala11Thr (chr16-83957702-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_182981.3(OSGIN1):c.31G>A(p.Ala11Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000548 in 1,605,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A11P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

OSGIN1
NM_182981.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.139

Publications

1 publications found

Variant links:

Genes affected

OSGIN1 (HGNC:30093): (oxidative stress induced growth inhibitor 1) This gene encodes an oxidative stress response protein that regulates cell death. Expression of the gene is regulated by p53 and is induced by DNA damage. The protein regulates apoptosis by inducing cytochrome c release from mitochondria. It also appears to be a key regulator of both inflammatory and anti-inflammatory molecules. The loss of this protein correlates with uncontrolled cell growth and tumor formation. Naturally occurring read-through transcription exists between this gene and the neighboring upstream malonyl-CoA decarboxylase (MLYCD) gene, but the read-through transcripts are unlikely to produce a protein product. [provided by RefSeq, Aug 2011]

OSGIN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03296292).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182981.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSGIN1	NM_182981.3	MANE Select	c.31G>A	p.Ala11Thr	missense	Exon 2 of 6	NP_892026.1	Q9UJX0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OSGIN1	ENST00000393306.6	TSL:1 MANE Select	c.31G>A	p.Ala11Thr	missense	Exon 2 of 6	ENSP00000376983.1	Q9UJX0
OSGIN1	ENST00000361711.7	TSL:2	c.31G>A	p.Ala11Thr	missense	Exon 2 of 6	ENSP00000355374.3	Q9UJX0
OSGIN1	ENST00000858442.1		c.31G>A	p.Ala11Thr	missense	Exon 3 of 7	ENSP00000528501.1

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

151954

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

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:

0.0000735

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000428

AC:

AN:

233440

AF XY:

0.0000473

show subpopulations

Gnomad AFR exome

AF:

0.000273

Gnomad AMR exome

AF:

0.0000600

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000384

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000454

AC:

AN:

1453912

Hom.:

Cov.:

AF XY:

0.0000457

AC XY:

AN XY:

722628

show subpopulations

African (AFR)

AF:

0.000271

AC:

AN:

33264

American (AMR)

AF:

0.0000455

AC:

AN:

43930

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25966

East Asian (EAS)

AF:

0.00

AC:

AN:

39256

South Asian (SAS)

AF:

0.0000235

AC:

AN:

85070

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0000451

AC:

AN:

1108038

Other (OTH)

AF:

0.0000500

AC:

AN:

60030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000145

AC:

AN:

151954

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74192

show subpopulations

African (AFR)

AF:

0.000218

AC:

AN:

41362

American (AMR)

AF:

0.000459

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

67998

Other (OTH)

AF:

0.000478

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000761

Hom.:

Bravo

AF:

0.000174

ExAC

AF:

0.0000331

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.29

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.00066

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.45

M_CAP

Benign

0.022

MetaRNN

Benign

0.033

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

-0.14

PrimateAI

Benign

0.31

PROVEAN

Benign

0.080

REVEL

Benign

0.011

Sift

Benign

0.76

Sift4G

Benign

0.61

Polyphen

0.0020

Vest4

0.12

MVP

0.22

MPC

0.089

ClinPred

0.0029

GERP RS

-2.3

Varity_R

0.014

gMVP

0.40

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over