Variant chr15-88639493-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002201.6(ISG20):c.127A>C(p.Ile43Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,154 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

ISG20
NM_002201.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.951

Variant links:

Genes affected

ISG20 (HGNC:6130): (interferon stimulated exonuclease gene 20) Enables 3'-5' exonuclease activity and RNA binding activity. Involved in defense response to virus; negative regulation of viral genome replication; and nucleobase-containing compound catabolic process. Located in cytoplasm and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

ISG20 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ISG20	NM_002201.6 link	c.127A>C	p.Ile43Leu	missense_variant	2/4	ENST00000306072.10	NP_002192.2	Q96AZ6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ISG20	ENST00000306072.10 link	c.127A>C	p.Ile43Leu	missense_variant	2/4	1	NM_002201.6	ENSP00000306565.5		Q96AZ6-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 17, 2024

The c.127A>C (p.I43L) alteration is located in exon 2 (coding exon 1) of the ISG20 gene. This alteration results from a A to C substitution at nucleotide position 127, causing the isoleucine (I) at amino acid position 43 to be replaced by a leucine (L). 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

Uncertain

0.56

BayesDel_addAF

Benign

-0.078

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.094

T;T;.;T

Eigen

Benign

0.15

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.50

LIST_S2

Uncertain

0.91

.;D;D;D

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.74

D;D;D;D

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.8

M;M;.;.

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.8

N;N;N;N

REVEL

Benign

0.20

Sift

Uncertain

0.0050

D;D;D;D

Sift4G

Uncertain

0.0050

D;D;D;D

Polyphen

0.39

B;B;.;.

Vest4

0.46

MutPred

0.88

Loss of catalytic residue at P45 (P = 0.0321);Loss of catalytic residue at P45 (P = 0.0321);Loss of catalytic residue at P45 (P = 0.0321);Loss of catalytic residue at P45 (P = 0.0321);

MVP

0.28

MPC

0.68

ClinPred

0.94

GERP RS

3.7

Varity_R

0.52

gMVP

0.75

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over