12-121033534-G-C

Variant names:

• chr12-121033534-G-C
• rs3213545
• NM_003733.4:c.408C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003733.4(OASL):​c.408C>G​(p.Leu136Leu) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: OASL NM_003733.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545
• Publications: 64 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-0.545 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003733.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OASL	NM_003733.4	MANE Select	c.408C>G	p.Leu136Leu	synonymous	Exon 2 of 6	NP_003724.1
	OASL	NM_001261825.2		c.408C>G	p.Leu136Leu	synonymous	Exon 2 of 4	NP_001248754.1
	OASL	NM_001395419.1		c.408C>G	p.Leu136Leu	synonymous	Exon 2 of 6	NP_001382348.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OASL	ENST00000257570.10	TSL:1 MANE Select	c.408C>G	p.Leu136Leu	synonymous	Exon 2 of 6	ENSP00000257570.4
	OASL	ENST00000620239.6	TSL:1	c.408C>G	p.Leu136Leu	synonymous	Exon 2 of 4	ENSP00000479512.1
	OASL	ENST00000339275.10	TSL:1	c.408C>G	p.Leu136Leu	synonymous	Exon 2 of 5	ENSP00000341125.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 18275

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.090
DANN	Benign	0.29
PhyloP100		-0.55

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

Other links and lift over

dbSNP: rs3213545; hg19: chr12-121471337;