16-83965316-C-G

Variant names:

• chr16-83965316-C-G
• rs201583830
• NM_182981.3:c.743C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_182981.3(OSGIN1):​c.743C>G​(p.Thr248Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000631 in 1,583,608 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. T248K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: OSGIN1 NM_182981.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.86
• 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]

NECAB2 (HGNC:23746): (N-terminal EF-hand calcium binding protein 2) The protein encoded by this gene is a neuronal calcium-binding protein that binds to and modulates the function of at least two receptors, adenosine A(2A) receptor and metabotropic glutamate receptor type 5. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.933

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.743C>G	p.Thr248Arg	missense	Exon 6 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.743C>G	p.Thr248Arg	missense	Exon 6 of 6	ENSP00000376983.1	Q9UJX0
	OSGIN1	ENST00000361711.7	TSL:2	c.743C>G	p.Thr248Arg	missense	Exon 6 of 6	ENSP00000355374.3	Q9UJX0
	OSGIN1	ENST00000858442.1		c.743C>G	p.Thr248Arg	missense	Exon 7 of 7	ENSP00000528501.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000559 AC: 8 AN: 1431282 Hom.: 0 Cov.: 34 AF XY: 0.00000565 AC XY: 4 AN XY: 708476

African (AFR) AF: 0.00 AC: 0 AN: 32968

American (AMR) AF: 0.00 AC: 0 AN: 43022

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24168

East Asian (EAS) AF: 0.000203 AC: 8 AN: 39334

South Asian (SAS) AF: 0.00 AC: 0 AN: 82690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5634

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1096318

Other (OTH) AF: 0.00 AC: 0 AN: 59078

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152326 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74478

African (AFR) AF: 0.0000241 AC: 1 AN: 41576

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000166 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Uncertain	0.099	D
BayesDel_noAF	Uncertain	0.080
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	-0.034	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		4.9
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.9	D
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.018	D
Polyphen		1.0	D
Vest4		0.81
MVP		0.89
MPC		0.51
ClinPred		0.98	D
GERP RS		3.8
Varity_R		0.63
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs201583830; hg19: chr16-83998921;