Genetic Variant OSGIN1:p.Ala274Gly (chr16-83965394-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_182981.3(OSGIN1):c.821C>G(p.Ala274Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000492 in 1,422,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A274V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

OSGIN1
NM_182981.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.140

Publications

0 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:

NECAB2 (HGNC:23746): (N-terminal EF-hand calcium binding protein 2) The protein encoded by this gene is a neuronal calcium-binding protein that binds to and modulates the function of at least two receptors, adenosine A(2A) receptor and metabotropic glutamate receptor type 5. [provided by RefSeq, Jul 2016]

NECAB2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21512562).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSGIN1	NM_182981.3 link	c.821C>G	p.Ala274Gly	missense_variant	Exon 6 of 6	ENST00000393306.6	NP_892026.1	Q9UJX0
NECAB2	XM_047434240.1 link	c.-23+158C>G		intron_variant	Intron 1 of 11		XP_047290196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OSGIN1	ENST00000393306.6 link	c.821C>G	p.Ala274Gly	missense_variant	Exon 6 of 6	1	NM_182981.3	ENSP00000376983.1	Q9UJX0
OSGIN1	ENST00000361711.7 link	c.821C>G	p.Ala274Gly	missense_variant	Exon 6 of 6	2		ENSP00000355374.3	Q9UJX0
OSGIN1	ENST00000343939.6 link	n.1453C>G		non_coding_transcript_exon_variant	Exon 7 of 7	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000492

AC:

AN:

1422438

Hom.:

Cov.:

AF XY:

0.00000568

AC XY:

AN XY:

703740

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33074

American (AMR)

AF:

0.00

AC:

AN:

43170

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23774

East Asian (EAS)

AF:

0.00

AC:

AN:

39372

South Asian (SAS)

AF:

0.00

AC:

AN:

80958

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42084

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5626

European-Non Finnish (NFE)

AF:

0.00000639

AC:

AN:

1095358

Other (OTH)

AF:

0.00

AC:

AN:

59022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

0.34

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.020

.;T;.

Eigen

Benign

-0.90

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.78

.;T;T

M_CAP

Pathogenic

0.33

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.3

.;M;.

PhyloP100

-0.14

PrimateAI

Benign

0.33

PROVEAN

Benign

-2.0

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.082

T;T;T

Sift4G

Benign

0.33

T;T;T

Polyphen

0.55

.;P;.

Vest4

0.15

MutPred

0.42

.;Loss of helix (P = 0.0444);.;

MVP

0.67

MPC

0.16

ClinPred

0.20

GERP RS

-1.6

Varity_R

0.070

gMVP

0.30

Mutation Taster

=97/3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over