NM_005101.4:c.237C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005101.4(ISG15):​c.237C>G​(p.Asp79Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D79D) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 35)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ISG15
NM_005101.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.32

Publications

2 publications found
Variant links:
Genes affected
ISG15 (HGNC:4053): (ISG15 ubiquitin like modifier) The protein encoded by this gene is a ubiquitin-like protein that is conjugated to intracellular target proteins upon activation by interferon-alpha and interferon-beta. Several functions have been ascribed to the encoded protein, including chemotactic activity towards neutrophils, direction of ligated target proteins to intermediate filaments, cell-to-cell signaling, and antiviral activity during viral infections. While conjugates of this protein have been found to be noncovalently attached to intermediate filaments, this protein is sometimes secreted. [provided by RefSeq, Dec 2012]
ISG15 Gene-Disease associations (from GenCC):
  • Mendelian susceptibility to mycobacterial diseases due to complete ISG15 deficiency
    Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.042057842).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ISG15NM_005101.4 linkc.237C>G p.Asp79Glu missense_variant Exon 2 of 2 ENST00000649529.1 NP_005092.1 P05161

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ISG15ENST00000649529.1 linkc.237C>G p.Asp79Glu missense_variant Exon 2 of 2 NM_005101.4 ENSP00000496832.1 P05161
ISG15ENST00000624697.4 linkc.213C>G p.Asp71Glu missense_variant Exon 3 of 3 3 ENSP00000485643.1 A0A096LPJ4
ISG15ENST00000624652.1 linkc.213C>G p.Asp71Glu missense_variant Exon 3 of 3 3 ENSP00000485313.1 A0A096LNZ9

Frequencies

GnomAD3 genomes
Cov.:
35
GnomAD2 exomes
AF:
0.00000400
AC:
1
AN:
250062
AF XY:
0.00000738
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461184
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726898
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33476
American (AMR)
AF:
0.0000224
AC:
1
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26130
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39696
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52800
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111954
Other (OTH)
AF:
0.00
AC:
0
AN:
60380
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
0.0050
DANN
Benign
0.44
DEOGEN2
Benign
0.0096
T;T;T;T
Eigen
Benign
-2.2
Eigen_PC
Benign
-2.4
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.44
T;T;.;T
M_CAP
Benign
0.0030
T
MetaRNN
Benign
0.042
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
.;.;L;L
PhyloP100
-3.3
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-0.34
.;.;N;.
REVEL
Benign
0.031
Sift
Benign
0.59
.;.;T;.
Sift4G
Benign
0.54
T;T;T;.
Polyphen
0.052
.;.;B;B
Vest4
0.049
MutPred
0.44
.;.;Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);
MVP
0.014
MPC
0.19
ClinPred
0.043
T
GERP RS
-8.0
Varity_R
0.23
gMVP
0.14
Mutation Taster
=99/1
polymorphism

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

Other links and lift over

dbSNP: rs61766284; hg19: chr1-949597; API