rs11195062

Positions:

• chr10-110277217-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130439.3(MXI1):​c.438-1963C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 152,040 control chromosomes in the GnomAD database, including 13,715 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 0.41 (13715 hom., cov: 32)
• Consequence: MXI1 NM_130439.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.692

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MXI1	NM_130439.3	c.438-1963C>A		intron_variant		ENST00000332674.9	NP_569157.2
MXI1	NM_001008541.1	c.99-1963C>A		intron_variant			NP_001008541.1
MXI1	NM_005962.5	c.237-1963C>A		intron_variant			NP_005953.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MXI1	ENST00000332674.9	c.438-1963C>A		intron_variant		1	NM_130439.3	ENSP00000331152

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62835 AN: 151922 Hom.: 13703 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.414 AC: 62900 AN: 152040 Hom.: 13715 Cov.: 32 AF XY: 0.421 AC XY: 31266 AN XY: 74346

Gnomad4 AFR AF: 0.445

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.649

Gnomad4 SAS AF: 0.703

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.427

Alfa AF: 0.372 Hom.: 17292

Bravo AF: 0.427

Asia WGS AF: 0.679 AC: 2363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.0
DANN	Benign	0.57

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

Other links and lift over

dbSNP: rs11195062; hg19: chr10-112036975;