12-121031561-C-A

Position:

• chr12-121031561-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003733.4(OASL):​c.538G>T​(p.Ala180Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OASL NM_003733.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.24

Genes affected

OASL (HGNC:8090): (2'-5'-oligoadenylate synthetase like) Enables DNA binding activity and double-stranded RNA binding activity. Involved in several processes, including interleukin-27-mediated signaling pathway; negative regulation of viral genome replication; and positive regulation of RIG-I signaling pathway. Located in cytosol; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24817744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OASL	NM_003733.4	c.538G>T	p.Ala180Ser	missense_variant	3/6	ENST00000257570.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OASL	ENST00000257570.10	c.538G>T	p.Ala180Ser	missense_variant	3/6	1	NM_003733.4	P1

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 specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2022

The c.538G>T (p.A180S) alteration is located in exon 3 (coding exon 3) of the OASL gene. This alteration results from a G to T substitution at nucleotide position 538, causing the alanine (A) at amino acid position 180 to be replaced by a serine (S). 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	Benign	0.10
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.49
DEOGEN2	Benign	0.015	T;.;.
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.67	T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.59	N;N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.050	N;.;N
REVEL	Benign	0.067
Sift	Benign	0.77	T;.;T
Sift4G	Benign	0.75	T;T;T
Polyphen		0.84	P;.;P
Vest4		0.39
MutPred		0.44		Gain of catalytic residue at G183 (P = 0);Gain of catalytic residue at G183 (P = 0);Gain of catalytic residue at G183 (P = 0);
MVP		0.44
MPC		0.47
ClinPred		0.63	D
GERP RS		3.7
Varity_R		0.11
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-121469364;