Variant 12-112907152-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016816.4(OAS1):c.113G>A(p.Cys38Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

OAS1
NM_016816.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.43

Variant links:

Genes affected

OAS1 (HGNC:8086): (2'-5'-oligoadenylate synthetase 1) This interferon-induced gene encodes a protein that synthesizes 2',5'-oligoadenylates (2-5As). This protein plays a key role in innate cellular antiviral response, and has been implicated in other cellular processes like cell growth and apoptosis. Alternative splicing results in multiple transcript variants with different enzymatic activities. Polymorphisms in this gene have been associated with susceptibility to viral infection, including SARS-CoV-2, and diabetes mellitus, type 1. This gene is located in a cluster of related genes on chromosome 12. [provided by RefSeq, May 2022]

OAS1 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	UniProt
OAS1	NM_016816.4 linkuse as main transcript	c.113G>A	p.Cys38Tyr	missense_variant	1/6	ENST00000202917.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OAS1	ENST00000202917.10 linkuse as main transcript	c.113G>A	p.Cys38Tyr	missense_variant	1/6	1	NM_016816.4	P2	P00973-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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 28, 2024

The c.113G>A (p.C38Y) alteration is located in exon 1 (coding exon 1) of the OAS1 gene. This alteration results from a G to A substitution at nucleotide position 113, causing the cysteine (C) at amino acid position 38 to be replaced by a tyrosine (Y). 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

0.67

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.29

T;.;.;T;.;.;.

Eigen

Uncertain

0.20

Eigen_PC

Benign

-0.0054

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.73

T;T;T;T;T;T;T

M_CAP

Benign

0.0093

MetaRNN

Uncertain

0.74

D;D;D;D;D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

2.9

M;M;M;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-9.1

D;D;D;D;D;D;D

REVEL

Benign

0.11

Sift

Uncertain

0.0020

D;D;D;D;D;D;D

Sift4G

Benign

0.076

T;T;T;D;T;D;T

Polyphen

1.0

D;D;D;.;D;.;.

Vest4

0.51

MutPred

0.66

Gain of methylation at K42 (P = 0.0521);Gain of methylation at K42 (P = 0.0521);Gain of methylation at K42 (P = 0.0521);Gain of methylation at K42 (P = 0.0521);Gain of methylation at K42 (P = 0.0521);Gain of methylation at K42 (P = 0.0521);.;

MVP

0.63

MPC

0.35

ClinPred

0.99

GERP RS

2.3

Varity_R

0.66

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over