Variant 10-110228257-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_130439.3(MXI1):c.343C>T(p.Pro115Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P115L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

MXI1
NM_130439.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.39

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12919739).

BP6

Variant 10-110228257-C-T is Benign according to our data. Variant chr10-110228257-C-T is described in ClinVar as [Benign]. Clinvar id is 2445275.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MXI1	NM_130439.3 linkuse as main transcript	c.343C>T	p.Pro115Ser	missense_variant	2/6	ENST00000332674.9
MXI1	NM_005962.5 linkuse as main transcript	c.142C>T	p.Pro48Ser	missense_variant	2/6
MXI1	NM_001008541.1 linkuse as main transcript	c.34C>T	p.Pro12Ser	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MXI1	ENST00000332674.9 linkuse as main transcript	c.343C>T	p.Pro115Ser	missense_variant	2/6	1	NM_130439.3		P50539-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Ovarian cancer

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University

Jan 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.15

Eigen_PC

Benign

0.0091

FATHMM_MKL

Benign

0.69

LIST_S2

Uncertain

0.86

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

M_CAP

Benign

0.0084

MetaRNN

Benign

0.13

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

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.60

D;D;D;D;N;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.53

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

REVEL

Benign

0.039

Sift

Benign

0.066

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

Sift4G

Benign

0.18

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

Polyphen

0.023

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

Vest4

0.29

MutPred

0.34

.;.;.;Gain of phosphorylation at P48 (P = 0.0019);Gain of phosphorylation at P48 (P = 0.0019);.;.;

MVP

0.13

MPC

0.58

ClinPred

0.31

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.082

gMVP

0.62

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over