NM_002462.5:c.24C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002462.5(MX1):​c.24C>G​(p.Ile8Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000246 in 1,461,798 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I8V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.000025 ( 1 hom. )

Consequence

MX1
NM_002462.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.52
Variant links:
Genes affected
MX1 (HGNC:7532): (MX dynamin like GTPase 1) This gene encodes a guanosine triphosphate (GTP)-metabolizing protein that participates in the cellular antiviral response. The encoded protein is induced by type I and type II interferons and antagonizes the replication process of several different RNA and DNA viruses. There is a related gene located adjacent to this gene on chromosome 21, and there are multiple pseudogenes located in a cluster on chromosome 4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.046801776).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MX1NM_002462.5 linkc.24C>G p.Ile8Met missense_variant Exon 5 of 17 ENST00000398598.8 NP_002453.2 P20591-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MX1ENST00000398598.8 linkc.24C>G p.Ile8Met missense_variant Exon 5 of 17 1 NM_002462.5 ENSP00000381599.3 P20591-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000636
AC:
16
AN:
251402
Hom.:
0
AF XY:
0.0000736
AC XY:
10
AN XY:
135886
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 SAS exome
AF:
0.000523
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000246
AC:
36
AN:
1461798
Hom.:
1
Cov.:
31
AF XY:
0.0000385
AC XY:
28
AN XY:
727214
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000406
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378
ExAC
AF:
0.0000576
AC:
7

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 12, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.24C>G (p.I8M) alteration is located in exon 7 (coding exon 1) of the MX1 gene. This alteration results from a C to G substitution at nucleotide position 24, causing the isoleucine (I) at amino acid position 8 to be replaced by a methionine (M). 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
Benign
0.068
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
0.013
DANN
Benign
0.34
DEOGEN2
Benign
0.11
T;.;T;T;T;.;T;T;.;T;.
Eigen
Benign
-2.0
Eigen_PC
Benign
-2.1
FATHMM_MKL
Benign
0.023
N
LIST_S2
Benign
0.71
.;T;T;T;.;T;T;T;T;T;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.047
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.46
T
MutationAssessor
Benign
1.3
L;.;.;L;L;.;.;.;.;.;L
PrimateAI
Benign
0.30
T
PROVEAN
Benign
0.33
N;N;D;N;N;N;N;N;D;N;.
REVEL
Benign
0.25
Sift
Benign
0.22
T;T;.;T;T;T;T;T;D;T;.
Sift4G
Benign
0.14
T;T;.;T;T;T;T;T;D;T;T
Polyphen
0.022
B;.;.;B;B;.;.;.;.;.;.
Vest4
0.17
MutPred
0.38
Gain of catalytic residue at I8 (P = 0.0026);Gain of catalytic residue at I8 (P = 0.0026);Gain of catalytic residue at I8 (P = 0.0026);Gain of catalytic residue at I8 (P = 0.0026);Gain of catalytic residue at I8 (P = 0.0026);Gain of catalytic residue at I8 (P = 0.0026);Gain of catalytic residue at I8 (P = 0.0026);Gain of catalytic residue at I8 (P = 0.0026);Gain of catalytic residue at I8 (P = 0.0026);Gain of catalytic residue at I8 (P = 0.0026);Gain of catalytic residue at I8 (P = 0.0026);
MVP
0.55
MPC
0.11
ClinPred
0.14
T
GERP RS
-5.8
Varity_R
0.058
gMVP
0.25

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs182413451; hg19: chr21-42804021; API