Genetic Variant NM_130439.3:c.412A>G (chr10-110244832-A-G) – 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.412A>G(p.Thr138Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MXI1
NM_130439.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.46

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:

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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=0.21544814).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MXI1	NM_130439.3	MANE Select	c.412A>G	p.Thr138Ala	missense	Exon 3 of 6	NP_569157.2	P50539-3
MXI1	NM_005962.5		c.211A>G	p.Thr71Ala	missense	Exon 3 of 6	NP_005953.4
MXI1	NM_001008541.1		c.98+16511A>G		intron	N/A	NP_001008541.1	P50539-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MXI1	ENST00000332674.9	TSL:1 MANE Select	c.412A>G	p.Thr138Ala	missense	Exon 3 of 6	ENSP00000331152.5	P50539-3
MXI1	ENST00000239007.11	TSL:1	c.211A>G	p.Thr71Ala	missense	Exon 3 of 6	ENSP00000239007.7	P50539-1
MXI1	ENST00000361248.8	TSL:1	c.98+16511A>G		intron	N/A	ENSP00000354606.4	P50539-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1448394

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719978

African (AFR)

AF:

0.00

AC:

AN:

32874

American (AMR)

AF:

0.00

AC:

AN:

43536

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25800

East Asian (EAS)

AF:

0.00

AC:

AN:

39118

South Asian (SAS)

AF:

0.00

AC:

AN:

84080

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52816

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4258

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106246

Other (OTH)

AF:

0.00

AC:

AN:

59666

GnomAD4 genome

Cov.:

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

0.20

BayesDel_addAF

Benign

-0.0032

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.71

Eigen

Benign

-0.10

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.75

M_CAP

Benign

0.015

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PhyloP100

5.5

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.6

REVEL

Benign

0.11

Sift

Benign

0.12

Sift4G

Benign

0.087

Polyphen

0.095

Vest4

0.56

MutPred

0.33

Loss of phosphorylation at T71 (P = 0.0256)

MVP

0.33

MPC

0.69

ClinPred

0.76

GERP RS

5.5

PromoterAI

-0.016

Neutral

(source)

Varity_R

0.26

gMVP

0.42

Mutation Taster

=73/27

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over