10-110285084-TAAAACAAAAC-TAAAAC

Variant names:

• chr10-110285084-TAAAAC-T
• rs16448
• NM_130439.3:c.*118_*122delAAAAC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_130439.3(MXI1):​c.*118_*122delAAAAC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 900,356 control chromosomes in the GnomAD database, including 107,123 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.44 (17448 hom., cov: 0)
  • Exomes 𝑓: 0.44 (89675 hom.)
• Consequence: MXI1 NM_130439.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.510
• Publications: 5 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.814 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MXI1	NM_130439.3	MANE Select	c.*118_*122delAAAAC		3_prime_UTR	Exon 6 of 6	NP_569157.2	P50539-3
	MXI1	NM_005962.5		c.*118_*122delAAAAC		3_prime_UTR	Exon 6 of 6	NP_005953.4
	MXI1	NM_001008541.1		c.*118_*122delAAAAC		3_prime_UTR	Exon 5 of 5	NP_001008541.1	P50539-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MXI1	ENST00000332674.9	TSL:1 MANE Select	c.*118_*122delAAAAC		3_prime_UTR	Exon 6 of 6	ENSP00000331152.5	P50539-3
	MXI1	ENST00000239007.11	TSL:1	c.*118_*122delAAAAC		3_prime_UTR	Exon 6 of 6	ENSP00000239007.7	P50539-1
	MXI1	ENST00000361248.8	TSL:1	c.*118_*122delAAAAC		3_prime_UTR	Exon 5 of 5	ENSP00000354606.4	P50539-4

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66476 AN: 151292 Hom.: 17448 Cov.: 0

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.453

GnomAD4 exome AF: 0.438 AC: 327877 AN: 748944 Hom.: 89675 AF XY: 0.442 AC XY: 165018 AN XY: 373294

African (AFR) AF: 0.0896 AC: 1924 AN: 21478

American (AMR) AF: 0.556 AC: 7172 AN: 12892

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 6380 AN: 14106

East Asian (EAS) AF: 0.816 AC: 22671 AN: 27786

South Asian (SAS) AF: 0.490 AC: 16669 AN: 34036

European-Finnish (FIN) AF: 0.535 AC: 19416 AN: 36266

Middle Eastern (MID) AF: 0.313 AC: 1045 AN: 3338

European-Non Finnish (NFE) AF: 0.421 AC: 237593 AN: 564544

Other (OTH) AF: 0.435 AC: 15007 AN: 34498

GnomAD4 genome AF: 0.439 AC: 66477 AN: 151412 Hom.: 17448 Cov.: 0 AF XY: 0.450 AC XY: 33242 AN XY: 73918

African (AFR) AF: 0.145 AC: 6029 AN: 41450

American (AMR) AF: 0.570 AC: 8668 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1682 AN: 3454

East Asian (EAS) AF: 0.835 AC: 4253 AN: 5096

South Asian (SAS) AF: 0.593 AC: 2853 AN: 4810

European-Finnish (FIN) AF: 0.575 AC: 5977 AN: 10402

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.525 AC: 35529 AN: 67702

Other (OTH) AF: 0.449 AC: 942 AN: 2096

Alfa AF: 0.316 Hom.: 895

Bravo AF: 0.427

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.51
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs16448; hg19: chr10-112044842; COSMIC: COSV53291792; COSMIC: COSV53291792;