Genetic Variant MXI1:p.Ala19Val (chr10-110207864-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_130439.3(MXI1):c.56C>T(p.Ala19Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000075 in 1,200,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

MXI1
NM_130439.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.459

Publications

0 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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10467735).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130439.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MXI1	NM_130439.3	MANE Select	c.56C>T	p.Ala19Val	missense	Exon 1 of 6	NP_569157.2	P50539-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MXI1	ENST00000332674.9	TSL:1 MANE Select	c.56C>T	p.Ala19Val	missense	Exon 1 of 6	ENSP00000331152.5	P50539-3
MXI1	ENST00000453116.5	TSL:5	c.56C>T	p.Ala19Val	missense	Exon 1 of 4	ENSP00000398981.1	F6U3F6
ENSG00000228417	ENST00000451656.1	TSL:3	n.456G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000268

AC:

AN:

149376

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000584

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000476

AC:

AN:

1050720

Hom.:

Cov.:

AF XY:

0.00000595

AC XY:

AN XY:

504168

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20268

American (AMR)

AF:

0.00

AC:

AN:

6138

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11304

East Asian (EAS)

AF:

0.0000505

AC:

AN:

19812

South Asian (SAS)

AF:

0.000119

AC:

AN:

25154

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25848

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2604

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

899978

Other (OTH)

AF:

0.0000252

AC:

AN:

39614

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000268

AC:

AN:

149484

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

72942

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41224

American (AMR)

AF:

0.00

AC:

AN:

15016

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3430

East Asian (EAS)

AF:

0.000585

AC:

AN:

5124

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9560

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

67012

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Benign

0.95

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.084

LIST_S2

Benign

0.66

M_CAP

Benign

0.063

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.1

PhyloP100

-0.46

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.40

REVEL

Benign

0.093

Sift

Benign

0.38

Sift4G

Benign

0.40

Polyphen

0.0

Vest4

0.11

MutPred

0.25

Loss of helix (P = 0.079)

MVP

0.28

MPC

0.56

ClinPred

0.87

GERP RS

-1.2

PromoterAI

-0.051

Neutral

(source)

gMVP

0.41

Mutation Taster

=96/4

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over