chr21-41436028-C-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002462.5(MX1):c.297C>A(p.Ser99Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,613,678 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000020 ( 0 hom. )
Consequence
MX1
NM_002462.5 missense, splice_region
NM_002462.5 missense, splice_region
Scores
7
8
4
Splicing: ADA: 0.00001584
2
Clinical Significance
Conservation
PhyloP100: -1.11
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 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 |
---|---|---|---|---|---|---|---|---|
MX1 | NM_002462.5 | c.297C>A | p.Ser99Arg | missense_variant, splice_region_variant | 6/17 | ENST00000398598.8 | NP_002453.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MX1 | ENST00000398598.8 | c.297C>A | p.Ser99Arg | missense_variant, splice_region_variant | 6/17 | 1 | NM_002462.5 | ENSP00000381599 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152228Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000360 AC: 9AN: 250218Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135286
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GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461450Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15AN XY: 726948
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GnomAD4 genome AF: 0.0000328 AC: 5AN: 152228Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74372
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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 | Dec 22, 2023 | The c.297C>A (p.S99R) alteration is located in exon 8 (coding exon 2) of the MX1 gene. This alteration results from a C to A substitution at nucleotide position 297, causing the serine (S) at amino acid position 99 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
DEOGEN2
Pathogenic
D;D;D;.;D;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
.;D;.;D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;H;H;.;.;H
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;D;.
REVEL
Pathogenic
Sift
Uncertain
D;D;D;D;D;.
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
D;D;D;.;.;.
Vest4
MutPred
Loss of glycosylation at S99 (P = 0.0211);Loss of glycosylation at S99 (P = 0.0211);Loss of glycosylation at S99 (P = 0.0211);Loss of glycosylation at S99 (P = 0.0211);Loss of glycosylation at S99 (P = 0.0211);Loss of glycosylation at S99 (P = 0.0211);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at