Variant 12-112941739-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006187.4(OAS3):c.347T>C(p.Leu116Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000219 in 1,461,712 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

OAS3
NM_006187.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.28

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:

OAS3 (HGNC:):

OAS3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OAS3	NM_006187.4 linkuse as main transcript	c.347T>C	p.Leu116Pro	missense_variant	2/16	ENST00000228928.12	NP_006178.2	Q9Y6K5
OAS3	NM_001410984.1 linkuse as main transcript	c.347T>C	p.Leu116Pro	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.347T>C	p.Leu116Pro	missense_variant	2/16	1	NM_006187.4	ENSP00000228928.7		Q9Y6K5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.000112

AC:

AN:

249242

Hom.:

AF XY:

0.0000888

AC XY:

AN XY:

135210

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000811

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:

0.0000219

AC:

AN:

1461712

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000715

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:

0.0000378

ExAC

AF:

0.0000661

AC:

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

Oct 20, 2024

The c.347T>C (p.L116P) alteration is located in exon 2 (coding exon 2) of the OAS3 gene. This alteration results from a T to C substitution at nucleotide position 347, causing the leucine (L) at amino acid position 116 to be replaced by a proline (P). 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

0.82

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.080

T;.;T

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.040

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.69

T;T;T

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.61

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.9

M;.;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.2

N;D;D

REVEL

Benign

0.23

Sift

Uncertain

0.0050

D;D;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.60

MutPred

0.68

Gain of catalytic residue at P112 (P = 4e-04);Gain of catalytic residue at P112 (P = 4e-04);Gain of catalytic residue at P112 (P = 4e-04);

MVP

0.29

MPC

0.70

ClinPred

0.31

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.73

gMVP

0.41

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