10-110243884-T-A

Variant names:

• chr10-110243884-T-A
• rs1418362
• NM_130439.3:c.408-944T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130439.3(MXI1):​c.408-944T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 151,958 control chromosomes in the GnomAD database, including 2,997 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (2997 hom., cov: 32)
• Consequence: MXI1 NM_130439.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• Publications: 1 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MXI1	NM_130439.3	MANE Select	c.408-944T>A		intron	N/A	NP_569157.2
	MXI1	NM_005962.5		c.207-944T>A		intron	N/A	NP_005953.4
	MXI1	NM_001008541.1		c.98+15563T>A		intron	N/A	NP_001008541.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MXI1	ENST00000332674.9	TSL:1 MANE Select	c.408-944T>A		intron	N/A	ENSP00000331152.5
	MXI1	ENST00000239007.11	TSL:1	c.207-944T>A		intron	N/A	ENSP00000239007.7
	MXI1	ENST00000361248.8	TSL:1	c.98+15563T>A		intron	N/A	ENSP00000354606.4

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29066 AN: 151840 Hom.: 2988 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.0879

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.194

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.192 AC: 29107 AN: 151958 Hom.: 2997 Cov.: 32 AF XY: 0.187 AC XY: 13911 AN XY: 74278

African (AFR) AF: 0.258 AC: 10717 AN: 41470

American (AMR) AF: 0.177 AC: 2690 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 393 AN: 3464

East Asian (EAS) AF: 0.0878 AC: 453 AN: 5162

South Asian (SAS) AF: 0.153 AC: 737 AN: 4824

European-Finnish (FIN) AF: 0.140 AC: 1485 AN: 10582

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11954 AN: 67900

Other (OTH) AF: 0.202 AC: 427 AN: 2110

Alfa AF: 0.189 Hom.: 353

Bravo AF: 0.198

Asia WGS AF: 0.174 AC: 608 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.1
DANN	Benign	0.83
PhyloP100		2.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs1418362; hg19: chr10-112003642;