Variant 10-110207952-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_130439.3(MXI1):c.144G>C(p.Arg48Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 1,593,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000097 ( 0 hom. )

Consequence

MXI1
NM_130439.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.89

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:

Genome browser will be placed here

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=0.05970493).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MXI1	NM_130439.3 linkuse as main transcript	c.144G>C	p.Arg48Ser	missense_variant	1/6	ENST00000332674.9	NP_569157.2	P50539-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MXI1	ENST00000332674.9 linkuse as main transcript	c.144G>C	p.Arg48Ser	missense_variant	1/6	1	NM_130439.3	ENSP00000331152.5	P50539-3
MXI1	ENST00000453116.5 linkuse as main transcript	c.144G>C	p.Arg48Ser	missense_variant	1/4	5		ENSP00000398981.1	F6U3F6
ENSG00000228417	ENST00000451656.1 linkuse as main transcript	n.368C>G		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151328

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD3 exomes

AF:

0.0000301

AC:

AN:

232430

Hom.:

AF XY:

0.0000237

AC XY:

AN XY:

126736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000445

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000971

AC:

AN:

1442030

Hom.:

Cov.:

AF XY:

0.00000837

AC XY:

AN XY:

717188

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000377

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151440

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74038

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2023

The c.144G>C (p.R48S) alteration is located in exon 1 (coding exon 1) of the MXI1 gene. This alteration results from a G to C substitution at nucleotide position 144, causing the arginine (R) at amino acid position 48 to be replaced by a serine (S). 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

-0.43

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.047

MetaRNN

Benign

0.060

T;T

MetaSVM

Benign

-1.1

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.17

N;N

REVEL

Benign

0.063

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.025

D;D

Polyphen

0.0010

B;.

Vest4

0.16

MutPred

0.46

Gain of glycosylation at R48 (P = 0.002);Gain of glycosylation at R48 (P = 0.002);

MVP

0.068

MPC

0.63

ClinPred

0.46

GERP RS

1.9

gMVP

0.33

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over