Variant chr12-121024131-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003733.4(OASL):c.906C>G(p.Ile302Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

OASL
NM_003733.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.789

Variant links:

Genes affected

OASL (HGNC:8090): (2'-5'-oligoadenylate synthetase like) Enables DNA binding activity and double-stranded RNA binding activity. Involved in several processes, including interleukin-27-mediated signaling pathway; negative regulation of viral genome replication; and positive regulation of RIG-I signaling pathway. Located in cytosol; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

OASL 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=0.13144478).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OASL	NM_003733.4 linkuse as main transcript	c.906C>G	p.Ile302Met	missense_variant	5/6	ENST00000257570.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OASL	ENST00000257570.10 linkuse as main transcript	c.906C>G	p.Ile302Met	missense_variant	5/6	1	NM_003733.4	P1	Q15646-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251152

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135742

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461734

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

May 24, 2023

The c.906C>G (p.I302M) alteration is located in exon 5 (coding exon 5) of the OASL gene. This alteration results from a C to G substitution at nucleotide position 906, causing the isoleucine (I) at amino acid position 302 to be replaced by a methionine (M). 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

0.15

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.99

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.33

M_CAP

Benign

0.066

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.83

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

-0.53

REVEL

Benign

0.024

Sift

Benign

0.15

Sift4G

Benign

0.51

Polyphen

0.082

Vest4

0.42

MutPred

0.34

Gain of catalytic residue at R227 (P = 9e-04);

MVP

0.50

ClinPred

0.73

GERP RS

3.8

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.

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