NM_130439.3:c.83C>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_130439.3(MXI1):c.83C>G(p.Pro28Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,365,504 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P28S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0026 ( 12 hom., cov: 31)

Exomes 𝑓: 0.0013 ( 30 hom. )

Consequence

MXI1
NM_130439.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.79

Publications

3 publications found

Variant links:

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]

MXI1 links:

ENSG00000228417 (HGNC:):

ENSG00000228417 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024390817).

BP6

Variant 10-110207891-C-G is Benign according to our data. Variant chr10-110207891-C-G is described in ClinVar as [Benign]. Clinvar id is 3037741.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00259 (388/149722) while in subpopulation EAS AF = 0.0476 (244/5126). AF 95% confidence interval is 0.0427. There are 12 homozygotes in GnomAd4. There are 214 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MXI1	NM_130439.3 link	c.83C>G	p.Pro28Arg	missense_variant	Exon 1 of 6	ENST00000332674.9	NP_569157.2	P50539-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MXI1	ENST00000332674.9 link	c.83C>G	p.Pro28Arg	missense_variant	Exon 1 of 6	1	NM_130439.3	ENSP00000331152.5	P50539-3
MXI1	ENST00000453116.5 link	c.83C>G	p.Pro28Arg	missense_variant	Exon 1 of 4	5		ENSP00000398981.1	F6U3F6
ENSG00000228417	ENST00000451656.1 link	n.429G>C		non_coding_transcript_exon_variant	Exon 3 of 3	3
ENSG00000303571	ENST00000795696.1 link	n.-67G>C		upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.00259

AC:

388

AN:

149614

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000532

Gnomad ASJ

AF:

0.000291

Gnomad EAS

AF:

0.0475

Gnomad SAS

AF:

0.00829

Gnomad FIN

AF:

0.00125

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000462

Gnomad OTH

AF:

0.00388

GnomAD2 exomes

AF:

0.00248

AC:

185

AN:

74482

AF XY:

0.00248

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000567

Gnomad ASJ exome

AF:

0.000896

Gnomad EAS exome

AF:

0.0493

Gnomad FIN exome

AF:

0.00144

Gnomad NFE exome

AF:

0.000436

Gnomad OTH exome

AF:

0.00258

GnomAD4 exome

AF:

0.00135

AC:

1636

AN:

1215782

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

830

AN XY:

598238

show subpopulations

African (AFR)

AF:

0.0000860

AC:

AN:

23250

American (AMR)

AF:

0.000335

AC:

AN:

14926

Ashkenazi Jewish (ASJ)

AF:

0.000581

AC:

AN:

18940

East Asian (EAS)

AF:

0.0346

AC:

820

AN:

23680

South Asian (SAS)

AF:

0.00514

AC:

301

AN:

58542

European-Finnish (FIN)

AF:

0.00170

AC:

AN:

41292

Middle Eastern (MID)

AF:

0.00118

AC:

AN:

3394

European-Non Finnish (NFE)

AF:

0.000185

AC:

182

AN:

984032

Other (OTH)

AF:

0.00505

AC:

241

AN:

47726

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

127

191

254

318

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00259

AC:

388

AN:

149722

Hom.:

Cov.:

AF XY:

0.00293

AC XY:

214

AN XY:

73114

show subpopulations

African (AFR)

AF:

0.00107

AC:

AN:

41310

American (AMR)

AF:

0.000531

AC:

AN:

15064

Ashkenazi Jewish (ASJ)

AF:

0.000291

AC:

AN:

3432

East Asian (EAS)

AF:

0.0476

AC:

244

AN:

5126

South Asian (SAS)

AF:

0.00829

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00125

AC:

AN:

9586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000462

AC:

AN:

67094

Other (OTH)

AF:

0.00384

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00114

Hom.:

Bravo

AF:

0.00210

ExAC

AF:

0.00233

AC:

253

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MXI1-related disorder

Benign:1

Sep 30, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.54

T;T

MetaRNN

Benign

0.0024

T;T

MetaSVM

Benign

-1.1

PhyloP100

1.8

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.18

N;N

REVEL

Benign

0.094

Sift

Uncertain

0.0060

D;D

Sift4G

Benign

0.72

T;T

Polyphen

0.98

D;.

Vest4

0.14

MVP

0.15

MPC

0.60

ClinPred

0.059

GERP RS

1.6

PromoterAI

0.014

Neutral

(source)

gMVP

0.18

Mutation Taster

=98/2

polymorphism

(source)

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

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NM_130439.3:c.83C>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over