chr16-83965345-C-T

Variant names:

• chr16-83965345-C-T
• NM_182981.3:c.772C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_182981.3(OSGIN1):​c.772C>T​(p.Pro258Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,418,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: OSGIN1 NM_182981.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.47
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41936702).

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.772C>T	p.Pro258Ser	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.772C>T	p.Pro258Ser	missense	Exon 6 of 6	ENSP00000376983.1	Q9UJX0
	OSGIN1	ENST00000361711.7	TSL:2	c.772C>T	p.Pro258Ser	missense	Exon 6 of 6	ENSP00000355374.3	Q9UJX0
	OSGIN1	ENST00000858442.1		c.772C>T	p.Pro258Ser	missense	Exon 7 of 7	ENSP00000528501.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1418990 Hom.: 0 Cov.: 34 AF XY: 0.00000285 AC XY: 2 AN XY: 701390

African (AFR) AF: 0.00 AC: 0 AN: 32852

American (AMR) AF: 0.00 AC: 0 AN: 42512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23412

East Asian (EAS) AF: 0.00 AC: 0 AN: 39336

South Asian (SAS) AF: 0.00 AC: 0 AN: 80134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43892

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5590

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1092494

Other (OTH) AF: 0.00 AC: 0 AN: 58768

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.67	T
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.36	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.5
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.31
Sift	Benign	0.26	T
Sift4G	Benign	0.35	T
Polyphen		0.84	P
Vest4		0.15
MutPred		0.46		Gain of glycosylation at P341 (P = 0.0112)
MVP		0.81
MPC		0.10
ClinPred		0.69	D
GERP RS		3.8
Varity_R		0.037
gMVP		0.34

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

hg19: chr16-83998950; COSMIC: COSV59419797; COSMIC: COSV59419797;