rs137852604
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4
The NM_130439.3(MXI1):c.362C>T(p.Ala121Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,614,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
MXI1
NM_130439.3 missense
NM_130439.3 missense
Scores
4
13
Clinical Significance
Conservation
PhyloP100: 2.42
Genes affected
MXI1 (HGNC:7534): (MAX interactor 1, dimerization protein) Expression of the c-myc gene, which produces an oncogenic transcription factor, is tightly regulated in normal cells but is frequently deregulated in human cancers. The protein encoded by this gene is a transcriptional repressor thought to negatively regulate MYC function, and is therefore a potential tumor suppressor. This protein inhibits the transcriptional activity of MYC by competing for MAX, another basic helix-loop-helix protein that binds to MYC and is required for its function. Defects in this gene are frequently found in patients with prostate tumors. Three alternatively spliced transcripts encoding different isoforms have been described. Additional alternatively spliced transcripts may exist but the products of these transcripts have not been verified experimentally. [provided by RefSeq, Jul 2008]
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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;
PP5
?
Variant 10-110228276-C-T is Pathogenic according to our data. Variant chr10-110228276-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 9537.Status of the report is no_assertion_criteria_provided, 0 stars.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.15656534).. Strength limited to SUPPORTING due to the PP5.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MXI1 | NM_130439.3 | c.362C>T | p.Ala121Val | missense_variant | 2/6 | ENST00000332674.9 | |
MXI1 | NM_005962.5 | c.161C>T | p.Ala54Val | missense_variant | 2/6 | ||
MXI1 | NM_001008541.1 | c.53C>T | p.Ala18Val | missense_variant | 2/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MXI1 | ENST00000332674.9 | c.362C>T | p.Ala121Val | missense_variant | 2/6 | 1 | NM_130439.3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152156Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251438Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135900
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461872Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727242
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152156Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74328
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Neurofibrosarcoma Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 1999 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
A;A;A;A;A;A;A
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N;N
REVEL
Benign
Sift
Benign
D;D;D;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T;T
Polyphen
P;.;.;B;B;.;D
Vest4
MutPred
0.24
.;.;.;Gain of methylation at K56 (P = 0.0977);Gain of methylation at K56 (P = 0.0977);.;.;
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
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