16-83965156-G-C

Variant names:

• chr16-83965156-G-C
• NM_182981.3:c.583G>C

Variant summary

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

The NM_182981.3(OSGIN1):​c.583G>C​(p.Gly195Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. G195S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: OSGIN1 NM_182981.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.91

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

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.583G>C	p.Gly195Arg	missense_variant	Exon 6 of 6	ENST00000393306.6	NP_892026.1
NECAB2	XM_047434240.1	c.-103G>C		upstream_gene_variant			XP_047290196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSGIN1	ENST00000393306.6	c.583G>C	p.Gly195Arg	missense_variant	Exon 6 of 6	1	NM_182981.3	ENSP00000376983.1
OSGIN1	ENST00000361711.7	c.583G>C	p.Gly195Arg	missense_variant	Exon 6 of 6	2		ENSP00000355374.3
OSGIN1	ENST00000343939.6	n.1215G>C		non_coding_transcript_exon_variant	Exon 7 of 7	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	.;T;.
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.084
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.66	.;T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.7	.;M;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.2	D;D;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.011	D;D;D
Sift4G	Uncertain	0.021	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.35
MutPred		0.62		.;Gain of MoRF binding (P = 0.011);.;
MVP		0.72
MPC		0.33
ClinPred		0.98	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr16-83998761;