rs3795737

Positions:

• chr1-156727264-T-C
• chr1-156727264-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370150.2(ISG20L2):​c.389A>G​(p.Asn130Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0785 in 1,613,996 control chromosomes in the GnomAD database, including 8,046 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N130H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.11 (1281 hom., cov: 32)
  • Exomes 𝑓: 0.075 (6765 hom.)
• Consequence: ISG20L2 NM_001370150.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.371

Genes affected

ISG20L2 (HGNC:25745): (interferon stimulated exonuclease gene 20 like 2) This gene encodes a 3'-5' exoribonuclease that may be involved in the processing of the 12S pre-rRNA. Pseudogenes have been identified on chromosomes 6 and 11. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003397286).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ISG20L2	NM_001370150.2	c.389A>G	p.Asn130Ser	missense_variant	2/4	ENST00000368219.2	NP_001357079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ISG20L2	ENST00000368219.2	c.389A>G	p.Asn130Ser	missense_variant	2/4	5	NM_001370150.2	ENSP00000357202.2

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16807 AN: 152050 Hom.: 1277 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0507

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0551

Gnomad OTH AF: 0.111

GnomAD3 exomes AF: 0.123 AC: 31009 AN: 251348 Hom.: 3482 AF XY: 0.112 AC XY: 15233 AN XY: 135890

Gnomad AFR exome AF: 0.180

Gnomad AMR exome AF: 0.362

Gnomad ASJ exome AF: 0.109

Gnomad EAS exome AF: 0.166

Gnomad SAS exome AF: 0.105

Gnomad FIN exome AF: 0.0491

Gnomad NFE exome AF: 0.0572

Gnomad OTH exome AF: 0.106

GnomAD4 exome AF: 0.0752 AC: 109897 AN: 1461828 Hom.: 6765 Cov.: 33 AF XY: 0.0745 AC XY: 54182 AN XY: 727216

Gnomad4 AFR exome AF: 0.177

Gnomad4 AMR exome AF: 0.347

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.138

Gnomad4 SAS exome AF: 0.107

Gnomad4 FIN exome AF: 0.0490

Gnomad4 NFE exome AF: 0.0559

Gnomad4 OTH exome AF: 0.0891

GnomAD4 genome AF: 0.111 AC: 16823 AN: 152168 Hom.: 1281 Cov.: 32 AF XY: 0.112 AC XY: 8306 AN XY: 74418

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.0507

Gnomad4 NFE AF: 0.0551

Gnomad4 OTH AF: 0.111

Alfa AF: 0.0787 Hom.: 560

Bravo AF: 0.131

TwinsUK AF: 0.0577 AC: 214

ALSPAC AF: 0.0545 AC: 210

ESP6500AA AF: 0.174 AC: 766

ESP6500EA AF: 0.0588 AC: 506

ExAC AF: 0.115 AC: 13914

Asia WGS AF: 0.154 AC: 534 AN: 3478

EpiCase AF: 0.0607

EpiControl AF: 0.0638

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.4
DANN	Benign	0.49
DEOGEN2	Benign	0.00080	T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.32	.;T
MetaRNN	Benign	0.0034	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.090	N;N
REVEL	Benign	0.048
Sift	Benign	0.39	T;T
Sift4G	Benign	0.87	T;T
Polyphen		0.0	B;B
Vest4		0.0070
MPC		0.23
ClinPred		0.0028	T
GERP RS		0.67
Varity_R		0.066
gMVP		0.12

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: rs3795737; hg19: chr1-156697056; COSMIC: COSV57459868; COSMIC: COSV57459868;