Variant 12-112938675-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.149

Variant links:

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]

OAS3 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 GnomAd4 at 20 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OAS3	NM_006187.4 linkuse as main transcript	c.145G>A	p.Ala49Thr	missense_variant	1/16	ENST00000228928.12	NP_006178.2
OAS3	NM_001410984.1 linkuse as main transcript	c.145G>A	p.Ala49Thr	missense_variant	1/16		NP_001397913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OAS3	ENST00000228928.12 linkuse as main transcript	c.145G>A	p.Ala49Thr	missense_variant	1/16	1	NM_006187.4	ENSP00000228928	P3
	ENST00000552784.1 linkuse as main transcript	n.354-29997C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00745

AC:

1134

AN:

152232

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00128

AC XY:

135

AN XY:

105204

show subpopulations

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.:

Cov.:

AF XY:

0.000643

AC XY:

456

AN XY:

709118

show subpopulations

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.:

Cov.:

AF XY:

0.00719

AC XY:

536

AN XY:

74504

show subpopulations

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.:

Bravo

AF:

0.00810

ESP6500AA

AF:

0.0211

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00189

AC:

223

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.62

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

LIST_S2

Benign

0.68

T;T;T

MetaRNN

Benign

0.0028

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.53

N;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.69

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over