Genetic Variant NM_130439.3:c.83C>A (chr10-110207891-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_130439.3(MXI1):c.83C>A(p.Pro28His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000879 in 1,365,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P28R) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

MXI1
NM_130439.3 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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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=0.17975277).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MXI1	NM_130439.3 link	c.83C>A	p.Pro28His	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>A	p.Pro28His	missense_variant	Exon 1 of 6	1	NM_130439.3	ENSP00000331152.5	P50539-3
MXI1	ENST00000453116.5 link	c.83C>A	p.Pro28His	missense_variant	Exon 1 of 4	5		ENSP00000398981.1	F6U3F6
ENSG00000228417	ENST00000451656.1 link	n.429G>T		non_coding_transcript_exon_variant	Exon 3 of 3	3
ENSG00000303571	ENST00000795696.1 link	n.-67G>T		upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

149616

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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

GnomAD2 exomes

AF:

0.0000134

AC:

AN:

74482

AF XY:

0.0000232

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000336

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000823

AC:

AN:

1215798

Hom.:

Cov.:

AF XY:

0.0000100

AC XY:

AN XY:

598246

show subpopulations

African (AFR)

AF:

0.0000430

AC:

AN:

23250

American (AMR)

AF:

0.00

AC:

AN:

14926

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18940

East Asian (EAS)

AF:

0.00

AC:

AN:

23692

South Asian (SAS)

AF:

0.00

AC:

AN:

58542

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41290

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3394

European-Non Finnish (NFE)

AF:

0.00000915

AC:

AN:

984032

Other (OTH)

AF:

0.00

AC:

AN:

47732

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000134

AC:

AN:

149724

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73116

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41310

American (AMR)

AF:

0.00

AC:

AN:

15064

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3432

East Asian (EAS)

AF:

0.00

AC:

AN:

5128

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

67094

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.650

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000921

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.069

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.48

T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-0.93

PhyloP100

1.8

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.58

N;N

REVEL

Benign

0.16

Sift

Uncertain

0.0020

D;D

Sift4G

Benign

0.12

T;T

Polyphen

0.99

D;.

Vest4

0.18

MutPred

0.098

Loss of glycosylation at P28 (P = 0.0251);Loss of glycosylation at P28 (P = 0.0251);

MVP

0.15

MPC

0.73

ClinPred

0.81

GERP RS

1.6

PromoterAI

-0.042

Neutral

(source)

gMVP

0.19

Mutation Taster

=97/3

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>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over