12-112907078-C-CCCA

Position:

• chr12-112907078-C-CCCA

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_016816.4(OAS1):​c.39_40insCCA​(p.Asp13_Lys14insPro) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OAS1 NM_016816.4 conservative_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.13

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_016816.4. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OAS1	NM_016816.4	c.39_40insCCA	p.Asp13_Lys14insPro	conservative_inframe_insertion	1/6	ENST00000202917.10	NP_058132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OAS1	ENST00000202917.10	c.39_40insCCA	p.Asp13_Lys14insPro	conservative_inframe_insertion	1/6	1	NM_016816.4	ENSP00000202917.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 17, 2021

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals with OAS1-related conditions. This variant is not present in population databases (ExAC no frequency). This variant, c.39_40insCCA, results in the insertion of 1 amino acid(s) to the OAS1 protein (p.Asp13_Lys14insPro), but otherwise preserves the integrity of the reading frame. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-113344883;