rs16448

Positions:

• chr10-110285084-TAAAACAAAAC-T
• chr10-110285084-TAAAACAAAAC-TAAAAC
• chr10-110285084-TAAAACAAAAC-TAAAACAAAACAAAAC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_130439.3(MXI1):​c.*113_*122del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000061 in 901,546 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000053 (0 hom.)
• Consequence: MXI1 NM_130439.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.42

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MXI1	NM_130439.3	c.*113_*122del		3_prime_UTR_variant	6/6	ENST00000332674.9
MXI1	NM_001008541.1	c.*113_*122del		3_prime_UTR_variant	5/5
MXI1	NM_005962.5	c.*113_*122del		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MXI1	ENST00000332674.9	c.*113_*122del		3_prime_UTR_variant	6/6	1	NM_130439.3

Frequencies

GnomAD3 genomes AF: 0.0000991 AC: 15 AN: 151422 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

Gnomad ASJ AF: 0.000290

Gnomad EAS AF: 0.000391

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000959

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000533 AC: 40 AN: 750004 Hom.: 0 AF XY: 0.0000508 AC XY: 19 AN XY: 373870

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000155

Gnomad4 ASJ exome AF: 0.000779

Gnomad4 EAS exome AF: 0.000108

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000389

Gnomad4 OTH exome AF: 0.0000579

GnomAD4 genome AF: 0.0000990 AC: 15 AN: 151542 Hom.: 0 Cov.: 0 AF XY: 0.000108 AC XY: 8 AN XY: 74000

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.000290

Gnomad4 EAS AF: 0.000392

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000959

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16448; hg19: chr10-112044842;