12-121020597-C-T

Position:

• chr12-121020597-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003733.4(OASL):​c.1509G>A​(p.Ser503=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,607,120 control chromosomes in the GnomAD database, including 25,088 homozygotes. 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: 𝑓 0.14 (1780 hom., cov: 32)
  • Exomes 𝑓: 0.17 (23308 hom.)
• Consequence: OASL NM_003733.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.509

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=0.509 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OASL	NM_003733.4	c.1509G>A	p.Ser503=	synonymous_variant	6/6	ENST00000257570.10	NP_003724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OASL	ENST00000257570.10	c.1509G>A	p.Ser503=	synonymous_variant	6/6	1	NM_003733.4	ENSP00000257570	P1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20571 AN: 152118 Hom.: 1779 Cov.: 32

Gnomad AFR AF: 0.0485

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.0820

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.116

GnomAD3 exomes AF: 0.149 AC: 37183 AN: 250174 Hom.: 3177 AF XY: 0.154 AC XY: 20830 AN XY: 135202

Gnomad AFR exome AF: 0.0442

Gnomad AMR exome AF: 0.0592

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.122

Gnomad SAS exome AF: 0.166

Gnomad FIN exome AF: 0.199

Gnomad NFE exome AF: 0.183

Gnomad OTH exome AF: 0.149

GnomAD4 exome AF: 0.175 AC: 254034 AN: 1454884 Hom.: 23308 Cov.: 32 AF XY: 0.175 AC XY: 126470 AN XY: 722342

Gnomad4 AFR exome AF: 0.0425

Gnomad4 AMR exome AF: 0.0639

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.105

Gnomad4 SAS exome AF: 0.165

Gnomad4 FIN exome AF: 0.192

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.162

GnomAD4 genome AF: 0.135 AC: 20577 AN: 152236 Hom.: 1780 Cov.: 32 AF XY: 0.136 AC XY: 10133 AN XY: 74432

Gnomad4 AFR AF: 0.0484

Gnomad4 AMR AF: 0.0819

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.115

Alfa AF: 0.172 Hom.: 5723

Bravo AF: 0.120

Asia WGS AF: 0.0980 AC: 340 AN: 3478

EpiCase AF: 0.185

EpiControl AF: 0.180

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.2
DANN	Benign	0.40

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: rs12819210; hg19: chr12-121458400; COSMIC: COSV56567435; COSMIC: COSV56567435;