16-83957708-A-C

Position:

• chr16-83957708-A-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_182981.3(OSGIN1):​c.37A>C​(p.Ser13Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00478 in 1,605,106 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0043 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0048 (18 hom.)
• Consequence: OSGIN1 NM_182981.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.481

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 Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003748864).
• BP6: Variant 16-83957708-A-C is Benign according to our data. Variant chr16-83957708-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 782018.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OSGIN1	NM_182981.3	c.37A>C	p.Ser13Arg	missense_variant	2/6	ENST00000393306.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OSGIN1	ENST00000393306.6	c.37A>C	p.Ser13Arg	missense_variant	2/6	1	NM_182981.3	P1

Frequencies

GnomAD3 genomes AF: 0.00426 AC: 647 AN: 151998 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00688

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.000661

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00587

Gnomad OTH AF: 0.00816

GnomAD3 exomes AF: 0.00405 AC: 940 AN: 232104 Hom.: 5 AF XY: 0.00427 AC XY: 538 AN XY: 126048

Gnomad AFR exome AF: 0.000759

Gnomad AMR exome AF: 0.00328

Gnomad ASJ exome AF: 0.0182

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00104

Gnomad FIN exome AF: 0.000979

Gnomad NFE exome AF: 0.00546

Gnomad OTH exome AF: 0.00544

GnomAD4 exome AF: 0.00483 AC: 7022 AN: 1452990 Hom.: 18 Cov.: 30 AF XY: 0.00486 AC XY: 3509 AN XY: 722152

Gnomad4 AFR exome AF: 0.000632

Gnomad4 AMR exome AF: 0.00383

Gnomad4 ASJ exome AF: 0.0189

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00119

Gnomad4 FIN exome AF: 0.00133

Gnomad4 NFE exome AF: 0.00525

Gnomad4 OTH exome AF: 0.00560

GnomAD4 genome AF: 0.00425 AC: 647 AN: 152116 Hom.: 4 Cov.: 32 AF XY: 0.00405 AC XY: 301 AN XY: 74354

Gnomad4 AFR AF: 0.00116

Gnomad4 AMR AF: 0.00688

Gnomad4 ASJ AF: 0.0187

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.000661

Gnomad4 NFE AF: 0.00587

Gnomad4 OTH AF: 0.00807

Alfa AF: 0.00587 Hom.: 1

Bravo AF: 0.00415

TwinsUK AF: 0.00431 AC: 16

ALSPAC AF: 0.00467 AC: 18

ESP6500AA AF: 0.000911 AC: 4

ESP6500EA AF: 0.00442 AC: 38

ExAC AF: 0.00363 AC: 438

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	OSGIN1: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	.;T;.;.;T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.54	.;T;T;T;T
MetaRNN	Benign	0.0037	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	.;M;.;.;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.3	N;N;N;.;N
REVEL	Benign	0.0090
Sift	Uncertain	0.0080	D;D;D;.;D
Sift4G	Benign	0.23	T;T;T;T;T
Polyphen		0.14	.;B;.;.;.
Vest4		0.38
MutPred		0.31		.;Gain of solvent accessibility (P = 0.005);.;.;.;
MVP		0.48
MPC		0.10
ClinPred		0.0080	T
GERP RS		0.50
Varity_R		0.064
gMVP		0.45

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: rs148139055; hg19: chr16-83991313;