12-112949145-T-G

Position:

• chr12-112949145-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 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

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OAS3	NM_006187.4	c.1314T>G	p.Ile438Met	missense_variant	6/16	ENST00000228928.12
OAS3	NM_001410984.1	c.1314T>G	p.Ile438Met	missense_variant	6/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OAS3	ENST00000228928.12	c.1314T>G	p.Ile438Met	missense_variant	6/16	1	NM_006187.4	P3
	ENST00000552784.1	n.354-40467A>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 69

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	1.0	P
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2285932; hg19: chr12-113386950;