12-112949145-T-G

Variant names:

• chr12-112949145-T-G
• rs2285932
• NM_006187.4:c.1314T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006187.4(OAS3):​c.1314T>G​(p.Ile438Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: OAS3 NM_006187.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.97
• Publications: 47 publications found

Genes affected

OAS3 (HGNC:8088): (2'-5'-oligoadenylate synthetase 3) This gene encodes an enzyme included in the 2', 5' oligoadenylate synthase family. This enzyme is induced by interferons and catalyzes the 2', 5' oligomers of adenosine in order to bind and activate RNase L. This enzyme family plays a significant role in the inhibition of cellular protein synthesis and viral infection resistance. [provided by RefSeq, Jul 2008]

ENSG00000257452 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1836038).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006187.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS3	NM_006187.4	MANE Select	c.1314T>G	p.Ile438Met	missense	Exon 6 of 16	NP_006178.2
	OAS3	NM_001410984.1		c.1314T>G	p.Ile438Met	missense	Exon 6 of 16	NP_001397913.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS3	ENST00000228928.12	TSL:1 MANE Select	c.1314T>G	p.Ile438Met	missense	Exon 6 of 16	ENSP00000228928.7
	OAS3	ENST00000679493.1		c.1314T>G	p.Ile438Met	missense	Exon 6 of 16	ENSP00000506397.1
	OAS3	ENST00000681346.1		c.1314T>G	p.Ile438Met	missense	Exon 6 of 17	ENSP00000505939.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 69

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.92
DANN	Benign	0.97
DEOGEN2	Benign	0.035	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0034	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		-4.0
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.95	P
Vest4		0.25
MutPred		0.56		Gain of catalytic residue at V434 (P = 0.0183)
MVP		0.12
MPC		0.18
ClinPred		0.84	D
GERP RS		-8.1
Varity_R		0.096
gMVP		0.21
Mutation Taster		=99/1	polymorphism

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: rs2285932; hg19: chr12-113386950;