dbSNP rs2084262721: OSGIN1:p.Leu226Val (chr16-83965249-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_182981.3(OSGIN1):c.676C>G(p.Leu226Val) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

OSGIN1
NM_182981.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.08

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.041880578).

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.676C>G	p.Leu226Val	missense	Exon 6 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.676C>G	p.Leu226Val	missense	Exon 6 of 6	ENSP00000376983.1	Q9UJX0
OSGIN1	ENST00000361711.7	TSL:2	c.676C>G	p.Leu226Val	missense	Exon 6 of 6	ENSP00000355374.3	Q9UJX0
OSGIN1	ENST00000858442.1		c.676C>G	p.Leu226Val	missense	Exon 7 of 7	ENSP00000528501.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

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

0.071

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

1.4

(source)

DANN

Benign

0.59

DEOGEN2

Benign

0.0026

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.26

M_CAP

Benign

0.010

MetaRNN

Benign

0.042

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.64

PhyloP100

-1.1

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.23

REVEL

Benign

0.019

Sift

Benign

0.36

Sift4G

Benign

0.37

Polyphen

0.0060

Vest4

0.065

MutPred

0.30

Gain of glycosylation at S306 (P = 0.0773)

MVP

0.092

MPC

0.096

ClinPred

0.071

GERP RS

-0.23

Varity_R

0.037

gMVP

0.15

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over