12-112965692-G-T

Variant names:

• chr12-112965692-G-T
• rs2240189
• NM_006187.4:c.2404-52G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006187.4(OAS3):​c.2404-52G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000216 in 1,390,418 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: OAS3 NM_006187.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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.2404-52G>T		intron	N/A	NP_006178.2
	OAS3	NM_001410984.1		c.2404-205G>T		intron	N/A	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.2404-52G>T		intron	N/A	ENSP00000228928.7	Q9Y6K5
	OAS3	ENST00000679493.1		c.2404-52G>T		intron	N/A	ENSP00000506397.1	A0A7P0TAU8
	OAS3	ENST00000681346.1		c.2404-52G>T		intron	N/A	ENSP00000505939.1	A0A7P0Z4F1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000216 AC: 3 AN: 1390418 Hom.: 0 AF XY: 0.00000292 AC XY: 2 AN XY: 685626

African (AFR) AF: 0.00 AC: 0 AN: 32294

American (AMR) AF: 0.00 AC: 0 AN: 39142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24132

East Asian (EAS) AF: 0.00 AC: 0 AN: 37946

South Asian (SAS) AF: 0.00 AC: 0 AN: 78536

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38634

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4066

European-Non Finnish (NFE) AF: 0.00000186 AC: 2 AN: 1077806

Other (OTH) AF: 0.0000173 AC: 1 AN: 57862

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.71
PhyloP100		-0.34

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: rs2240189; hg19: chr12-113403497;