OAS1 p.Gly397*

Variant names:

• chr12-112916738-GGT-TAA
• NM_016816.4:c.884_884+2delGGTinsTAA
• OAS1 p.Arg295Met

Your query was ambiguous. Multiple possible variants found:

• chr12-112916738-GGT-TAA
• chr12-112916738-GGT-TGA
• chr12-112919637-G-T
• chr12-112916738-GGT-TAG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_016816.4(OAS1):​c.884_884+2delGGTinsTAA​(p.Arg295Met) variant causes a splice donor, missense, splice region, intron change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OAS1 NM_016816.4 splice_donor, missense, splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.94
• Publications: 0 publications found

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)

ENSG00000257452 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS1	NM_016816.4	MANE Select	c.884_884+2delGGTinsTAA	p.Arg295Met	splice_donor missense splice_region intron	N/A	NP_058132.2	P00973-1
	OAS1	NM_001032409.3		c.884_884+2delGGTinsTAA	p.Arg295Met	splice_donor missense splice_region intron	N/A	NP_001027581.1	P00973-3
	OAS1	NM_001406020.1		c.860_860+2delGGTinsTAA	p.Arg287Met	splice_donor missense splice_region intron	N/A	NP_001392949.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS1	ENST00000202917.10	TSL:1 MANE Select	c.884_884+2delGGTinsTAA	p.Arg295Met	splice_donor missense splice_region intron	N/A	ENSP00000202917.5	P00973-1
	OAS1	ENST00000445409.7	TSL:1	c.884_884+2delGGTinsTAA	p.Arg295Met	splice_donor missense splice_region intron	N/A	ENSP00000388001.2	P00973-3
	OAS1	ENST00000540589.3	TSL:1	c.884_884+2delGGTinsTAA	p.Arg295Met	splice_donor missense splice_region intron	N/A	ENSP00000474083.2	S4R3A5

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.9

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-113354543;