12-112970403-G-C

Variant names:

• chr12-112970403-G-C
• rs2010604
• NM_006187.4:c.*430G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006187.4(OAS3):​c.*430G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 221,938 control chromosomes in the GnomAD database, including 63,006 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 0.76 (44519 hom., cov: 33)
  • Exomes 𝑓: 0.72 (18487 hom.)
• Consequence: OAS3 NM_006187.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.433
• Publications: 21 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS3	NM_006187.4	MANE Select	c.*430G>C		3_prime_UTR	Exon 16 of 16	NP_006178.2
	OAS3	NM_001410984.1		c.*430G>C		3_prime_UTR	Exon 16 of 16	NP_001397913.1	A0A7P0T8S7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS3	ENST00000228928.12	TSL:1 MANE Select	c.*430G>C		3_prime_UTR	Exon 16 of 16	ENSP00000228928.7	Q9Y6K5
	OAS3	ENST00000679493.1		c.*269G>C		3_prime_UTR	Exon 16 of 16	ENSP00000506397.1	A0A7P0TAU8
	OAS3	ENST00000681346.1		c.*444G>C		3_prime_UTR	Exon 17 of 17	ENSP00000505939.1	A0A7P0Z4F1

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115433 AN: 152058 Hom.: 44472 Cov.: 33

Gnomad AFR AF: 0.874

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.773

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.723

GnomAD4 exome AF: 0.722 AC: 50382 AN: 69762 Hom.: 18487 Cov.: 0 AF XY: 0.723 AC XY: 26218 AN XY: 36242

African (AFR) AF: 0.867 AC: 2236 AN: 2578

American (AMR) AF: 0.796 AC: 3246 AN: 4080

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 995 AN: 1758

East Asian (EAS) AF: 0.916 AC: 3576 AN: 3902

South Asian (SAS) AF: 0.750 AC: 5639 AN: 7520

European-Finnish (FIN) AF: 0.780 AC: 2072 AN: 2658

Middle Eastern (MID) AF: 0.628 AC: 186 AN: 296

European-Non Finnish (NFE) AF: 0.689 AC: 29839 AN: 43308

Other (OTH) AF: 0.708 AC: 2593 AN: 3662

GnomAD4 genome AF: 0.759 AC: 115541 AN: 152176 Hom.: 44519 Cov.: 33 AF XY: 0.765 AC XY: 56914 AN XY: 74394

African (AFR) AF: 0.874 AC: 36295 AN: 41530

American (AMR) AF: 0.772 AC: 11805 AN: 15292

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

East Asian (EAS) AF: 0.910 AC: 4706 AN: 5170

South Asian (SAS) AF: 0.774 AC: 3733 AN: 4826

European-Finnish (FIN) AF: 0.774 AC: 8193 AN: 10592

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.686 AC: 46640 AN: 67980

Other (OTH) AF: 0.719 AC: 1520 AN: 2114

Alfa AF: 0.646 Hom.: 1911

Bravo AF: 0.764

Asia WGS AF: 0.824 AC: 2866 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.2
DANN	Benign	0.66
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs2010604; hg19: chr12-113408208;