Variant chr12-112941785-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000228928.12(OAS3):c.393C>G(p.Phe131Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

OAS3
ENST00000228928.12 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.692

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06862995).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OAS3	NM_006187.4 linkuse as main transcript	c.393C>G	p.Phe131Leu	missense_variant	2/16	ENST00000228928.12	NP_006178.2
OAS3	NM_001410984.1 linkuse as main transcript	c.393C>G	p.Phe131Leu	missense_variant	2/16		NP_001397913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OAS3	ENST00000228928.12 linkuse as main transcript	c.393C>G	p.Phe131Leu	missense_variant	2/16	1	NM_006187.4	ENSP00000228928	P3
	ENST00000552784.1 linkuse as main transcript	n.354-33107G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000161

AC:

AN:

249092

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461708

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000894

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 22, 2024

The c.393C>G (p.F131L) alteration is located in exon 2 (coding exon 2) of the OAS3 gene. This alteration results from a C to G substitution at nucleotide position 393, causing the phenylalanine (F) at amino acid position 131 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.016

T;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.59

T;T;T

M_CAP

Benign

0.0099

MetaRNN

Benign

0.069

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.0

N;D;D

REVEL

Benign

0.10

Sift

Benign

0.035

D;T;T

Sift4G

Benign

0.17

T;T;T

Polyphen

0.023

B;B;B

Vest4

0.064

MutPred

0.61

Gain of catalytic residue at R132 (P = 0.0079);Gain of catalytic residue at R132 (P = 0.0079);Gain of catalytic residue at R132 (P = 0.0079);

MVP

0.040

MPC

0.14

ClinPred

0.043

GERP RS

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.36

gMVP

0.31

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