16-83957708-A-C

Variant names:

• chr16-83957708-A-C
• rs148139055
• NM_182981.3:c.37A>C

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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
• Publications: 3 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: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 782018.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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.37A>C	p.Ser13Arg	missense	Exon 2 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.37A>C	p.Ser13Arg	missense	Exon 2 of 6	ENSP00000376983.1	Q9UJX0
	OSGIN1	ENST00000361711.7	TSL:2	c.37A>C	p.Ser13Arg	missense	Exon 2 of 6	ENSP00000355374.3	Q9UJX0
	OSGIN1	ENST00000858442.1		c.37A>C	p.Ser13Arg	missense	Exon 3 of 7	ENSP00000528501.1

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

GnomAD2 exomes AF: 0.00405 AC: 940 AN: 232104 AF XY: 0.00427

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 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

African (AFR) AF: 0.000632 AC: 21 AN: 33240

American (AMR) AF: 0.00383 AC: 168 AN: 43852

Ashkenazi Jewish (ASJ) AF: 0.0189 AC: 491 AN: 25972

East Asian (EAS) AF: 0.00 AC: 0 AN: 39212

South Asian (SAS) AF: 0.00119 AC: 101 AN: 84932

European-Finnish (FIN) AF: 0.00133 AC: 70 AN: 52532

Middle Eastern (MID) AF: 0.00330 AC: 19 AN: 5760

European-Non Finnish (NFE) AF: 0.00525 AC: 5816 AN: 1107494

Other (OTH) AF: 0.00560 AC: 336 AN: 59996

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

African (AFR) AF: 0.00116 AC: 48 AN: 41522

American (AMR) AF: 0.00688 AC: 105 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4810

European-Finnish (FIN) AF: 0.000661 AC: 7 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00587 AC: 399 AN: 67990

Other (OTH) AF: 0.00807 AC: 17 AN: 2106

Alfa AF: 0.00552 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

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.0037	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.48
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.0090
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.23	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
Mutation Taster		=95/5	polymorphism

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: rs148139055; hg19: chr16-83991313;