Genetic Variant OAS1:p.Arg361Lys (chr12-112919432-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016816.4(OAS1):c.1082G>A(p.Arg361Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R361T) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Consequence

OAS1
NM_016816.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.37

Publications

54 publications found

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 Gene-Disease associations (from GenCC):

pulmonary alveolar proteinosis with hypogammaglobulinemia
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

OAS1 links:

ENSG00000257452 (HGNC:):

ENSG00000257452 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.046613872).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016816.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OAS1	NM_016816.4	MANE Select	c.1082G>A	p.Arg361Lys	missense	Exon 6 of 6	NP_058132.2	P00973-1
OAS1	NM_001406021.1		c.1058G>A	p.Arg353Lys	missense	Exon 6 of 6	NP_001392950.1	A0A7P0Z4N8
OAS1	NM_001406027.1		c.608G>A	p.Arg203Lys	missense	Exon 4 of 4	NP_001392956.1	A0A7P0T8F9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OAS1	ENST00000202917.10	TSL:1 MANE Select	c.1082G>A	p.Arg361Lys	missense	Exon 6 of 6	ENSP00000202917.5	P00973-1
OAS1	ENST00000552526.2	TSL:1	c.1082G>A	p.Arg361Lys	missense splice_region	Exon 6 of 7	ENSP00000475139.2	S4R467
OAS1	ENST00000452357.7	TSL:1	c.*1675G>A		3_prime_UTR	Exon 5 of 5	ENSP00000415721.2	P00973-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.3

(source)

DANN

Benign

0.45

DEOGEN2

Benign

0.014

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0090

LIST_S2

Benign

0.36

M_CAP

Benign

0.0015

MetaRNN

Benign

0.047

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

PhyloP100

-2.4

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.030

REVEL

Benign

0.0040

Sift

Benign

0.42

Sift4G

Benign

0.92

Polyphen

0.0

Vest4

0.065

MutPred

0.34

Gain of methylation at R361 (P = 0.0044)

MVP

0.17

ClinPred

0.020

GERP RS

-4.5

Varity_R

0.033

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over