12-121020597-C-T

Variant names:

• chr12-121020597-C-T
• rs12819210
• NM_003733.4:c.1509G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003733.4(OASL):​c.1509G>A​(p.Ser503Ser) 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
• Publications: 37 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: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OASL	NM_003733.4	MANE Select	c.1509G>A	p.Ser503Ser	synonymous	Exon 6 of 6	NP_003724.1	Q15646-1
	OASL	NM_001261825.2		c.1119G>A	p.Ser373Ser	synonymous	Exon 4 of 4	NP_001248754.1	Q15646-3
	OASL	NM_198213.3		c.*499G>A		3_prime_UTR	Exon 5 of 5	NP_937856.1	Q15646-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OASL	ENST00000257570.10	TSL:1 MANE Select	c.1509G>A	p.Ser503Ser	synonymous	Exon 6 of 6	ENSP00000257570.4	Q15646-1
	OASL	ENST00000620239.6	TSL:1	c.1119G>A	p.Ser373Ser	synonymous	Exon 4 of 4	ENSP00000479512.1	Q15646-3
	OASL	ENST00000339275.10	TSL:1	c.*499G>A		3_prime_UTR	Exon 5 of 5	ENSP00000341125.5	Q15646-2

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

GnomAD2 exomes AF: 0.149 AC: 37183 AN: 250174 AF XY: 0.154

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 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

African (AFR) AF: 0.0425 AC: 1413 AN: 33274

American (AMR) AF: 0.0639 AC: 2833 AN: 44336

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 3120 AN: 25988

East Asian (EAS) AF: 0.105 AC: 4132 AN: 39492

South Asian (SAS) AF: 0.165 AC: 14223 AN: 86032

European-Finnish (FIN) AF: 0.192 AC: 10226 AN: 53368

Middle Eastern (MID) AF: 0.108 AC: 621 AN: 5736

European-Non Finnish (NFE) AF: 0.188 AC: 207720 AN: 1106640

Other (OTH) AF: 0.162 AC: 9746 AN: 60018

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

African (AFR) AF: 0.0484 AC: 2011 AN: 41568

American (AMR) AF: 0.0819 AC: 1251 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 426 AN: 3472

East Asian (EAS) AF: 0.126 AC: 650 AN: 5174

South Asian (SAS) AF: 0.158 AC: 763 AN: 4828

European-Finnish (FIN) AF: 0.190 AC: 2009 AN: 10588

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12994 AN: 68004

Other (OTH) AF: 0.115 AC: 243 AN: 2116

Alfa AF: 0.168 Hom.: 11088

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.2
DANN	Benign	0.40
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism (auto)

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