10-110286442-G-T

Position:

• chr10-110286442-G-T

Variant summary

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

The NM_130439.3(MXI1):​c.*1455G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0431 in 150,854 control chromosomes in the GnomAD database, including 415 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 0.043 (415 hom., cov: 30)
  • Exomes 𝑓: 0.0023 (0 hom.)
• Consequence: MXI1 NM_130439.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.69

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=-0.54).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MXI1	NM_130439.3	c.*1455G>T		3_prime_UTR_variant	6/6	ENST00000332674.9	NP_569157.2
MXI1	NM_005962.5	c.*1455G>T		3_prime_UTR_variant	6/6		NP_005953.4
MXI1	NM_001008541.1	c.*1455G>T		3_prime_UTR_variant	5/5		NP_001008541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MXI1	ENST00000332674.9	c.*1455G>T		3_prime_UTR_variant	6/6	1	NM_130439.3	ENSP00000331152.5

Frequencies

GnomAD3 genomes AF: 0.0434 AC: 6518 AN: 150306 Hom.: 417 Cov.: 30

Gnomad AFR AF: 0.0278

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0359

Gnomad ASJ AF: 0.0438

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.00826

Gnomad MID AF: 0.0801

Gnomad NFE AF: 0.0286

Gnomad OTH AF: 0.0466

GnomAD4 exome AF: 0.00230 AC: 1 AN: 434 Hom.: 0 Cov.: 0 AF XY: 0.00382 AC XY: 1 AN XY: 262

Gnomad4 FIN exome AF: 0.00235

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0433 AC: 6508 AN: 150420 Hom.: 415 Cov.: 30 AF XY: 0.0477 AC XY: 3489 AN XY: 73188

Gnomad4 AFR AF: 0.0278

Gnomad4 AMR AF: 0.0358

Gnomad4 ASJ AF: 0.0438

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.00826

Gnomad4 NFE AF: 0.0286

Gnomad4 OTH AF: 0.0465

Alfa AF: 0.0335 Hom.: 241

Bravo AF: 0.0409

Asia WGS AF: 0.232 AC: 805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	10
DANN	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1803997; hg19: chr10-112046200;