chr12-112938675-G-A

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

1
17

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]

Genome browser will be placed here

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
OAS3NM_006187.4 linkuse as main transcriptc.145G>A p.Ala49Thr missense_variant 1/16 ENST00000228928.12 NP_006178.2
OAS3NM_001410984.1 linkuse as main transcriptc.145G>A p.Ala49Thr missense_variant 1/16 NP_001397913.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OAS3ENST00000228928.12 linkuse as main transcriptc.145G>A p.Ala49Thr missense_variant 1/161 NM_006187.4 ENSP00000228928 P3
ENST00000552784.1 linkuse as main transcriptn.354-29997C>T intron_variant, non_coding_transcript_variant 4

Frequencies

GnomAD3 genomes
AF:
0.00745
AC:
1134
AN:
152232
Hom.:
20
Cov.:
34
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.:
6
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.:
11
Cov.:
37
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.:
20
Cov.:
34
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.:
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:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJun 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

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

Other links and lift over

dbSNP: rs62623451; hg19: chr12-113376480; API