NM_130439.3:c.160A>G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_130439.3(MXI1):c.160A>G(p.Ile54Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000277 in 1,443,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

MXI1
NM_130439.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.97

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15756276).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MXI1	NM_130439.3 link	c.160A>G	p.Ile54Val	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.160A>G	p.Ile54Val	missense_variant	Exon 1 of 6	1	NM_130439.3	ENSP00000331152.5	P50539-3
MXI1	ENST00000453116.5 link	c.160A>G	p.Ile54Val	missense_variant	Exon 1 of 4	5		ENSP00000398981.1	F6U3F6
ENSG00000228417	ENST00000451656.1 link	n.352T>C		non_coding_transcript_exon_variant	Exon 3 of 3	3
ENSG00000303571	ENST00000795696.1 link	n.-144T>C		upstream_gene_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000277

AC:

AN:

1443002

Hom.:

Cov.:

AF XY:

0.00000557

AC XY:

AN XY:

717860

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32064

American (AMR)

AF:

0.00

AC:

AN:

42684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25642

East Asian (EAS)

AF:

0.00

AC:

AN:

37532

South Asian (SAS)

AF:

0.0000355

AC:

AN:

84408

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52684

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5568

European-Non Finnish (NFE)

AF:

9.07e-7

AC:

AN:

1102924

Other (OTH)

AF:

0.00

AC:

AN:

59496

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 29, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.160A>G (p.I54V) alteration is located in exon 1 (coding exon 1) of the MXI1 gene. This alteration results from a A to G substitution at nucleotide position 160, causing the isoleucine (I) at amino acid position 54 to be replaced by a valine (V). 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

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.0052

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-1.1

PhyloP100

5.0

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

0.12

N;N

REVEL

Benign

0.049

Sift

Benign

0.35

T;T

Sift4G

Benign

0.69

T;T

Polyphen

0.11

B;.

Vest4

0.088

MutPred

0.24

Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);

MVP

0.23

MPC

0.46

ClinPred

0.95

GERP RS

4.9

PromoterAI

-0.071

Neutral

(source)

gMVP

0.19

Mutation Taster

=83/17

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.160A>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over