chr10-110286442-G-T

Variant names:

• chr10-110286442-G-T
• rs1803997
• ENST00000485566.2:n.2270G>T

Variant summary

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

The ENST00000485566.2(MXI1):​n.2270G>T variant causes a non coding transcript exon 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 ENST00000485566.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.69
• Publications: 6 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=-0.54).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000485566.2. 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.*1455G>T		3_prime_UTR	Exon 6 of 6	NP_569157.2
	MXI1	NM_005962.5		c.*1455G>T		3_prime_UTR	Exon 6 of 6	NP_005953.4
	MXI1	NM_001008541.1		c.*1455G>T		3_prime_UTR	Exon 5 of 5	NP_001008541.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MXI1	ENST00000485566.2	TSL:1	n.2270G>T		non_coding_transcript_exon	Exon 4 of 4
	MXI1	ENST00000332674.9	TSL:1 MANE Select	c.*1455G>T		3_prime_UTR	Exon 6 of 6	ENSP00000331152.5
	MXI1	ENST00000239007.11	TSL:1	c.*1455G>T		3_prime_UTR	Exon 6 of 6	ENSP00000239007.7

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00235 AC: 1 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AF: 0.00 AC: 0 AN: 4

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.0278 AC: 1137 AN: 40930

American (AMR) AF: 0.0358 AC: 540 AN: 15076

Ashkenazi Jewish (ASJ) AF: 0.0438 AC: 152 AN: 3468

East Asian (EAS) AF: 0.280 AC: 1436 AN: 5130

South Asian (SAS) AF: 0.230 AC: 1096 AN: 4772

European-Finnish (FIN) AF: 0.00826 AC: 82 AN: 9930

Middle Eastern (MID) AF: 0.0862 AC: 25 AN: 290

European-Non Finnish (NFE) AF: 0.0286 AC: 1939 AN: 67830

Other (OTH) AF: 0.0465 AC: 97 AN: 2084

Alfa AF: 0.0344 Hom.: 680

Bravo AF: 0.0409

Asia WGS AF: 0.232 AC: 805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	10
DANN	Benign	0.81
PhyloP100		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs1803997; hg19: chr10-112046200;