12-112919404-G-T

Position:

• chr12-112919404-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016816.4(OAS1):​c.1054G>T​(p.Ala352Ser) 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. 15/19 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. A352T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: OAS1 NM_016816.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117

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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04311022).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OAS1	NM_016816.4	c.1054G>T	p.Ala352Ser	missense_variant	6/6	ENST00000202917.10	NP_058132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OAS1	ENST00000202917.10	c.1054G>T	p.Ala352Ser	missense_variant	6/6	1	NM_016816.4	ENSP00000202917	P2
	ENST00000552784.1	n.354-10726C>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.073
DANN	Benign	0.58
DEOGEN2	Benign	0.014	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0066	N
LIST_S2	Benign	0.40	T;.
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.043	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.12	N;.
REVEL	Benign	0.022
Sift	Benign	0.65	T;.
Sift4G	Benign	0.59	T;.
Polyphen		0.0	B;.
Vest4		0.10
MutPred		0.23		Gain of glycosylation at A352 (P = 0.0184);.;
MVP		0.23
ClinPred		0.055	T
GERP RS		-1.4
Varity_R		0.071

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

Other links and lift over

dbSNP: rs1131476; hg19: chr12-113357209;