16-83960596-G-C

Variant names:

• chr16-83960596-G-C
• NM_182981.3:c.232G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_182981.3(OSGIN1):​c.232G>C​(p.Glu78Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,058 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OSGIN1 NM_182981.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.94

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSGIN1	NM_182981.3	c.232G>C	p.Glu78Gln	missense_variant	Exon 4 of 6	ENST00000393306.6	NP_892026.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSGIN1	ENST00000393306.6	c.232G>C	p.Glu78Gln	missense_variant	Exon 4 of 6	1	NM_182981.3	ENSP00000376983.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461058 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726802

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	.;T;.;.;T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	.;D;D;D;D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.55	D;D;D;D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Pathogenic	3.1	.;M;.;.;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.7	D;D;D;.;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0030	D;D;D;.;D
Sift4G	Uncertain	0.010	D;D;D;D;D
Polyphen		1.0	.;D;.;.;.
Vest4		0.83
MutPred		0.57		.;Loss of phosphorylation at S164 (P = 0.1034);.;.;.;
MVP		0.53
MPC		0.49
ClinPred		0.97	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.43
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-83994201;