12-112949145-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006187.4(OAS3):​c.1314T>C​(p.Ile438Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 1,613,512 control chromosomes in the GnomAD database, including 412,362 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.78 (47406 hom., cov: 30)
  • Exomes 𝑓: 0.70 (364956 hom.)
• Consequence: OAS3 NM_006187.4 synonymous
• 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP7: Synonymous conserved (PhyloP=-3.97 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

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>C	p.Ile438Ile	synonymous	Exon 6 of 16	NP_006178.2
	OAS3	NM_001410984.1		c.1314T>C	p.Ile438Ile	synonymous	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>C	p.Ile438Ile	synonymous	Exon 6 of 16	ENSP00000228928.7
	OAS3	ENST00000679493.1		c.1314T>C	p.Ile438Ile	synonymous	Exon 6 of 16	ENSP00000506397.1
	OAS3	ENST00000681346.1		c.1314T>C	p.Ile438Ile	synonymous	Exon 6 of 17	ENSP00000505939.1

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118533 AN: 151828 Hom.: 47341 Cov.: 30

Gnomad AFR AF: 0.945

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.789

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.733

GnomAD2 exomes AF: 0.756 AC: 186601 AN: 246878 AF XY: 0.747

Gnomad AFR exome AF: 0.950

Gnomad AMR exome AF: 0.834

Gnomad ASJ exome AF: 0.557

Gnomad EAS exome AF: 0.921

Gnomad FIN exome AF: 0.801

Gnomad NFE exome AF: 0.691

Gnomad OTH exome AF: 0.701

GnomAD4 exome AF: 0.703 AC: 1027429 AN: 1461566 Hom.: 364956 Cov.: 69 AF XY: 0.703 AC XY: 511403 AN XY: 727068

African (AFR) AF: 0.952 AC: 31874 AN: 33480

American (AMR) AF: 0.826 AC: 36951 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 14691 AN: 26136

East Asian (EAS) AF: 0.901 AC: 35761 AN: 39700

South Asian (SAS) AF: 0.759 AC: 65455 AN: 86256

European-Finnish (FIN) AF: 0.794 AC: 42333 AN: 53300

Middle Eastern (MID) AF: 0.634 AC: 3655 AN: 5768

European-Non Finnish (NFE) AF: 0.678 AC: 754119 AN: 1111832

Other (OTH) AF: 0.705 AC: 42590 AN: 60372

GnomAD4 genome AF: 0.781 AC: 118662 AN: 151946 Hom.: 47406 Cov.: 30 AF XY: 0.786 AC XY: 58329 AN XY: 74228

African (AFR) AF: 0.945 AC: 39167 AN: 41460

American (AMR) AF: 0.781 AC: 11919 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1905 AN: 3472

East Asian (EAS) AF: 0.909 AC: 4660 AN: 5128

South Asian (SAS) AF: 0.775 AC: 3725 AN: 4806

European-Finnish (FIN) AF: 0.789 AC: 8332 AN: 10554

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.686 AC: 46645 AN: 67948

Other (OTH) AF: 0.736 AC: 1549 AN: 2106

Alfa AF: 0.706 Hom.: 58082

Bravo AF: 0.788

Asia WGS AF: 0.856 AC: 2977 AN: 3478

EpiCase AF: 0.671

EpiControl AF: 0.676

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.34
DANN	Benign	0.53
PhyloP100		-4.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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; COSMIC: COSV108004446; COSMIC: COSV108004446;