16-83960735-G-C

Variant names:

• chr16-83960735-G-C
• rs747452671
• NM_182981.3:c.371G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_182981.3(OSGIN1):​c.371G>C​(p.Arg124Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R124Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: OSGIN1 NM_182981.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.786

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.371G>C	p.Arg124Pro	missense	Exon 4 of 6	NP_892026.1	Q9UJX0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSGIN1	ENST00000393306.6	TSL:1 MANE Select	c.371G>C	p.Arg124Pro	missense	Exon 4 of 6	ENSP00000376983.1	Q9UJX0
	OSGIN1	ENST00000361711.7	TSL:2	c.371G>C	p.Arg124Pro	missense	Exon 4 of 6	ENSP00000355374.3	Q9UJX0
	OSGIN1	ENST00000858442.1		c.371G>C	p.Arg124Pro	missense	Exon 5 of 7	ENSP00000528501.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152236 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460950 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726746

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111960

Other (OTH) AF: 0.0000166 AC: 1 AN: 60374

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152236 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74372

African (AFR) AF: 0.00 AC: 0 AN: 41470

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68048

Other (OTH) AF: 0.00 AC: 0 AN: 2090

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.3
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.20
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.99	D
Vest4		0.76
MutPred		0.42		Gain of relative solvent accessibility (P = 0.09)
MVP		0.57
MPC		0.55
ClinPred		0.98	D
GERP RS		3.9
Varity_R		0.67
gMVP		0.71

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

Other links and lift over

dbSNP: rs747452671; hg19: chr16-83994340;