21-41443804-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_002462.5(MX1):c.946G>A(p.Gly316Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,614,238 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0080 ( 19 hom., cov: 33)
Exomes 𝑓: 0.00096 ( 12 hom. )
Consequence
MX1
NM_002462.5 missense
NM_002462.5 missense
Scores
1
3
13
Clinical Significance
Conservation
PhyloP100: 1.48
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 Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.008124739).
BP6
?
Variant 21-41443804-G-A is Benign according to our data. Variant chr21-41443804-G-A is described in ClinVar as [Benign]. Clinvar id is 711249.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00796 (1213/152366) while in subpopulation AFR AF= 0.0265 (1102/41572). AF 95% confidence interval is 0.0252. There are 19 homozygotes in gnomad4. There are 575 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 20 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MX1 | NM_002462.5 | c.946G>A | p.Gly316Arg | missense_variant | 11/17 | ENST00000398598.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MX1 | ENST00000398598.8 | c.946G>A | p.Gly316Arg | missense_variant | 11/17 | 1 | NM_002462.5 | P1 | |
ENST00000411427.3 | n.220-1058C>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00798 AC: 1215AN: 152248Hom.: 20 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00242 AC: 608AN: 251486Hom.: 8 AF XY: 0.00193 AC XY: 262AN XY: 135916
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GnomAD4 exome AF: 0.000958 AC: 1401AN: 1461872Hom.: 12 Cov.: 30 AF XY: 0.000866 AC XY: 630AN XY: 727244
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GnomAD4 genome ? AF: 0.00796 AC: 1213AN: 152366Hom.: 19 Cov.: 33 AF XY: 0.00772 AC XY: 575AN XY: 74514
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ESP6500AA
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | May 24, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Uncertain
D;D;D;D;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;.;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;D;D;.
REVEL
Uncertain
Sift
Benign
D;D;D;D;.
Sift4G
Benign
T;T;T;T;T
Polyphen
P;P;P;.;.
Vest4
MutPred
Gain of phosphorylation at T319 (P = 0.1145);Gain of phosphorylation at T319 (P = 0.1145);Gain of phosphorylation at T319 (P = 0.1145);.;Gain of phosphorylation at T319 (P = 0.1145);
MVP
MPC
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at