12-112938675-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006187.4(OAS3):c.145G>A(p.Ala49Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,582,552 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0074 (20 hom., cov: 34)
  • Exomes 𝑓: 0.00076 (11 hom.)
• Consequence: OAS3 NM_006187.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.149

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0028470457).
• BP6: Variant 12-112938675-G-A is Benign according to our data. Variant chr12-112938675-G-A is described in ClinVar as [Benign]. Clinvar id is 786934.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00743 (1132/152350) while in subpopulation AFR AF= 0.026 (1083/41582). AF 95% confidence interval is 0.0248. There are 20 homozygotes in gnomad4. There are 536 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 20 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OAS3	NM_006187.4	c.145G>A	p.Ala49Thr	missense_variant	1/16	ENST00000228928.12
OAS3	NM_001410984.1	c.145G>A	p.Ala49Thr	missense_variant	1/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OAS3	ENST00000228928.12	c.145G>A	p.Ala49Thr	missense_variant	1/16	1	NM_006187.4	P3
	ENST00000552784.1	n.354-29997C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00745 AC: 1134 AN: 152232 Hom.: 20 Cov.: 34

Gnomad AFR AF: 0.0261

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00175 AC: 333 AN: 190694 Hom.: 6 AF XY: 0.00128 AC XY: 135 AN XY: 105204

Gnomad AFR exome AF: 0.0265

Gnomad AMR exome AF: 0.00159

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000379

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000610

Gnomad OTH exome AF: 0.000602

GnomAD4 exome AF: 0.000762 AC: 1090 AN: 1430202 Hom.: 11 Cov.: 37 AF XY: 0.000643 AC XY: 456 AN XY: 709118

Gnomad4 AFR exome AF: 0.0283

Gnomad4 AMR exome AF: 0.00181

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000155

Gnomad4 OTH exome AF: 0.00132

GnomAD4 genome AF: 0.00743 AC: 1132 AN: 152350 Hom.: 20 Cov.: 34 AF XY: 0.00719 AC XY: 536 AN XY: 74504

Gnomad4 AFR AF: 0.0260

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00106 Hom.: 0

Bravo AF: 0.00810

ESP6500AA AF: 0.0211 AC: 77

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00189 AC: 223

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	7.3
Dann	Benign	0.64
DEOGEN2	Benign	0.011	T;.;T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.68	T;T;T
MetaRNN	Benign	0.0028	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.53	N;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.46	N;N;N
REVEL	Benign	0.056
Sift	Benign	0.49	T;T;T
Sift4G	Benign	0.89	T;T;T
Polyphen		0.0040	B;B;B
Vest4		0.17
MVP		0.19
MPC		0.11
ClinPred		0.0065	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.041
gMVP		0.065

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: rs62623451; hg19: chr12-113376480;