chr12-112949145-T-C

Position:

• chr12-112949145-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006187.4(OAS3):​c.1314T>C​(p.Ile438=) 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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OAS3	NM_006187.4	c.1314T>C	p.Ile438=	synonymous_variant	6/16	ENST00000228928.12
OAS3	NM_001410984.1	c.1314T>C	p.Ile438=	synonymous_variant	6/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OAS3	ENST00000228928.12	c.1314T>C	p.Ile438=	synonymous_variant	6/16	1	NM_006187.4	P3
	ENST00000552784.1	n.354-40467A>G		intron_variant, non_coding_transcript_variant		4

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

GnomAD3 exomes AF: 0.756 AC: 186601 AN: 246878 Hom.: 71848 AF XY: 0.747 AC XY: 100214 AN XY: 134154

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 SAS exome AF: 0.752

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

Gnomad4 AFR exome AF: 0.952

Gnomad4 AMR exome AF: 0.826

Gnomad4 ASJ exome AF: 0.562

Gnomad4 EAS exome AF: 0.901

Gnomad4 SAS exome AF: 0.759

Gnomad4 FIN exome AF: 0.794

Gnomad4 NFE exome AF: 0.678

Gnomad4 OTH exome AF: 0.705

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

Gnomad4 AFR AF: 0.945

Gnomad4 AMR AF: 0.781

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.909

Gnomad4 SAS AF: 0.775

Gnomad4 FIN AF: 0.789

Gnomad4 NFE AF: 0.686

Gnomad4 OTH AF: 0.736

Alfa AF: 0.695 Hom.: 44949

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.34
DANN	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs2285932; hg19: chr12-113386950;