16-83957702-G-T

Variant names:

• chr16-83957702-G-T
• rs781547435
• NM_182981.3:c.31G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_182981.3(OSGIN1):​c.31G>T​(p.Ala11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: OSGIN1 NM_182981.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055440992).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSGIN1	NM_182981.3	c.31G>T	p.Ala11Ser	missense_variant	Exon 2 of 6	ENST00000393306.6	NP_892026.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSGIN1	ENST00000393306.6	c.31G>T	p.Ala11Ser	missense_variant	Exon 2 of 6	1	NM_182981.3	ENSP00000376983.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000428 AC: 1 AN: 233440 Hom.: 0 AF XY: 0.00000789 AC XY: 1 AN XY: 126728

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000961

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453914 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 722628

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: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.17
DANN	Benign	0.54
DEOGEN2	Benign	0.00089	.;T;.;.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.45	.;T;T;T;T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.055	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	.;L;.;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.13	N;N;N;.;N
REVEL	Benign	0.022
Sift	Benign	0.52	T;T;T;.;T
Sift4G	Benign	0.69	T;T;T;T;T
Polyphen		0.14	.;B;.;.;.
Vest4		0.23
MutPred		0.16		.;Gain of phosphorylation at A94 (P = 0.018);.;.;.;
MVP		0.22
MPC		0.086
ClinPred		0.031	T
GERP RS		-2.3
Varity_R		0.024
gMVP		0.41

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

LitVar

Other links and lift over

dbSNP: rs781547435; hg19: chr16-83991307;