NM_130439.3:c.344C>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM1BP4_Strong

The NM_130439.3(MXI1):c.344C>T(p.Pro115Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,614,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P115S) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

MXI1
NM_130439.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.76

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM1

In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 3 uncertain in NM_130439.3

BP4

Computational evidence support a benign effect (MetaRNN=0.0384005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MXI1	NM_130439.3 link	c.344C>T	p.Pro115Leu	missense_variant	Exon 2 of 6	ENST00000332674.9	NP_569157.2	P50539-3
MXI1	NM_005962.5 link	c.143C>T	p.Pro48Leu	missense_variant	Exon 2 of 6		NP_005953.4	P50539-1
MXI1	NM_001008541.1 link	c.35C>T	p.Pro12Leu	missense_variant	Exon 2 of 5		NP_001008541.1	P50539-4A0A0S2Z3X5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MXI1	ENST00000332674.9 link	c.344C>T	p.Pro115Leu	missense_variant	Exon 2 of 6	1	NM_130439.3	ENSP00000331152.5		P50539-3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000756

AC:

AN:

251448

AF XY:

0.0000809

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000979

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.000277

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112006

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41446

American (AMR)

AF:

0.0000655

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000578

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 07, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.344C>T (p.P115L) alteration is located in exon 2 (coding exon 2) of the MXI1 gene. This alteration results from a C to T substitution at nucleotide position 344, causing the proline (P) at amino acid position 115 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

.;.;.;T;T;.;.

Eigen

Benign

-0.11

Eigen_PC

Benign

0.038

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.90

D;D;D;D;D;D;D

M_CAP

Benign

0.0094

MetaRNN

Benign

0.038

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.72

.;.;.;N;.;.;.

PhyloP100

1.8

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.0

N;N;N;N;N;N;N

REVEL

Benign

0.051

Sift

Uncertain

0.013

D;T;D;D;T;D;D

Sift4G

Uncertain

0.032

D;T;D;T;T;T;T

Polyphen

0.0080

B;.;.;B;B;.;P

Vest4

0.25

MutPred

0.34

.;.;.;Loss of catalytic residue at P47 (P = 0.0131);Loss of catalytic residue at P47 (P = 0.0131);.;.;

MVP

0.10

MPC

0.57

ClinPred

0.071

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.61

Mutation Taster

=80/20

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.344C>T

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