12-112941669-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006187.4(OAS3):​c.277C>T​(p.Arg93Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

OAS3
NM_006187.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.92
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06429693).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OAS3NM_006187.4 linkuse as main transcriptc.277C>T p.Arg93Cys missense_variant 2/16 ENST00000228928.12 NP_006178.2 Q9Y6K5
OAS3NM_001410984.1 linkuse as main transcriptc.277C>T p.Arg93Cys missense_variant 2/16 NP_001397913.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OAS3ENST00000228928.12 linkuse as main transcriptc.277C>T p.Arg93Cys missense_variant 2/161 NM_006187.4 ENSP00000228928.7 Q9Y6K5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000241
AC:
6
AN:
249264
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
135224
show subpopulations
Gnomad AFR exome
AF:
0.000129
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000464
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000130
AC:
19
AN:
1461712
Hom.:
0
Cov.:
31
AF XY:
0.0000138
AC XY:
10
AN XY:
727138
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000189
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

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 submitterclinical testingAmbry GeneticsJul 10, 2024The c.277C>T (p.R93C) alteration is located in exon 2 (coding exon 2) of the OAS3 gene. This alteration results from a C to T substitution at nucleotide position 277, causing the arginine (R) at amino acid position 93 to be replaced by a cysteine (C). 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
Benign
0.14
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
8.9
DANN
Benign
0.90
DEOGEN2
Benign
0.018
T;.;T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.0099
N
LIST_S2
Benign
0.68
T;T;T
M_CAP
Benign
0.0051
T
MetaRNN
Benign
0.064
T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.3
L;.;.
PrimateAI
Benign
0.21
T
PROVEAN
Benign
-0.64
N;D;D
REVEL
Benign
0.0090
Sift
Benign
0.11
T;T;T
Sift4G
Benign
0.15
T;D;T
Polyphen
0.0020
B;B;B
Vest4
0.13
MutPred
0.50
Gain of catalytic residue at R91 (P = 0.0228);Gain of catalytic residue at R91 (P = 0.0228);Gain of catalytic residue at R91 (P = 0.0228);
MVP
0.16
MPC
0.16
ClinPred
0.016
T
GERP RS
-3.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.20
gMVP
0.19

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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.

Other links and lift over

dbSNP: rs748860456; hg19: chr12-113379474; API