10-110207894-C-T

Variant names:

• chr10-110207894-C-T
• rs753454623
• NM_130439.3:c.86C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_130439.3(MXI1):​c.86C>T​(p.Ala29Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000798 in 1,378,198 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 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000073 (0 hom.)
• Consequence: MXI1 NM_130439.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.569
• Publications: 0 publications found

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]

ENSG00000228417 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008906096).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MXI1	NM_130439.3	c.86C>T	p.Ala29Val	missense_variant	Exon 1 of 6	ENST00000332674.9	NP_569157.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MXI1	ENST00000332674.9	c.86C>T	p.Ala29Val	missense_variant	Exon 1 of 6	1	NM_130439.3	ENSP00000331152.5
MXI1	ENST00000453116.5	c.86C>T	p.Ala29Val	missense_variant	Exon 1 of 4	5		ENSP00000398981.1
ENSG00000228417	ENST00000451656.1	n.426G>A		non_coding_transcript_exon_variant	Exon 3 of 3	3
ENSG00000303571	ENST00000795696.1	n.-70G>A		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0000134 AC: 2 AN: 149688 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000133

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000600 AC: 5 AN: 83396 AF XY: 0.0000416

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000610

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000733 AC: 9 AN: 1228510 Hom.: 0 Cov.: 30 AF XY: 0.00000991 AC XY: 6 AN XY: 605176

African (AFR) AF: 0.00 AC: 0 AN: 23766

American (AMR) AF: 0.000555 AC: 9 AN: 16214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19332

East Asian (EAS) AF: 0.00 AC: 0 AN: 24514

South Asian (SAS) AF: 0.00 AC: 0 AN: 60046

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42088

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3446

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 990750

Other (OTH) AF: 0.00 AC: 0 AN: 48354

GnomAD4 genome AF: 0.0000134 AC: 2 AN: 149688 Hom.: 0 Cov.: 31 AF XY: 0.0000137 AC XY: 1 AN XY: 73030

African (AFR) AF: 0.00 AC: 0 AN: 41190

American (AMR) AF: 0.000133 AC: 2 AN: 15038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3438

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67126

Other (OTH) AF: 0.00 AC: 0 AN: 2064

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000710 AC: 8

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 11, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.86C>T (p.A29V) alteration is located in exon 1 (coding exon 1) of the MXI1 gene. This alteration results from a C to T substitution at nucleotide position 86, causing the alanine (A) at amino acid position 29 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	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Uncertain	1.0
Eigen	Benign	-0.048
Eigen_PC	Benign	-0.078
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.59	T;T
MetaRNN	Benign	0.0089	T;T
MetaSVM	Benign	-1.0	T
PhyloP100		0.57
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.68	N;N
REVEL	Benign	0.090
Sift	Benign	0.091	T;T
Sift4G	Benign	0.084	T;T
Polyphen		0.88	P;.
Vest4		0.18
MutPred		0.14		Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);
MVP		0.41
MPC		0.57
ClinPred		0.89	D
GERP RS		2.3
PromoterAI		-0.050	Neutral
gMVP		0.20
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs753454623; hg19: chr10-111967652;