NM_130439.3:c.274+5499C>T

Variant names:

• chr10-110213581-C-T
• rs1342273
• NM_130439.3:c.274+5499C>T

Variant summary

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

The NM_130439.3(MXI1):​c.274+5499C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,058 control chromosomes in the GnomAD database, including 6,053 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 0.25 (6053 hom., cov: 32)
• Consequence: MXI1 NM_130439.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.753
• 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]

LOC105378480 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.451 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MXI1	NM_130439.3	MANE Select	c.274+5499C>T		intron	N/A	NP_569157.2
	MXI1	NM_001008541.1		c.-36+3266C>T		intron	N/A	NP_001008541.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MXI1	ENST00000332674.9	TSL:1 MANE Select	c.274+5499C>T		intron	N/A	ENSP00000331152.5
	MXI1	ENST00000361248.8	TSL:1	c.-36+3266C>T		intron	N/A	ENSP00000354606.4
	MXI1	ENST00000453116.5	TSL:5	c.274+5499C>T		intron	N/A	ENSP00000398981.1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37817 AN: 151940 Hom.: 6031 Cov.: 32

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0825

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.249 AC: 37893 AN: 152058 Hom.: 6053 Cov.: 32 AF XY: 0.243 AC XY: 18081 AN XY: 74340

African (AFR) AF: 0.456 AC: 18915 AN: 41444

American (AMR) AF: 0.198 AC: 3023 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 437 AN: 3472

East Asian (EAS) AF: 0.0823 AC: 426 AN: 5178

South Asian (SAS) AF: 0.163 AC: 786 AN: 4822

European-Finnish (FIN) AF: 0.139 AC: 1471 AN: 10576

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12070 AN: 67976

Other (OTH) AF: 0.242 AC: 510 AN: 2106

Alfa AF: 0.201 Hom.: 10277

Bravo AF: 0.264

Asia WGS AF: 0.190 AC: 662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.1
DANN	Benign	0.69
PhyloP100		0.75
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: rs1342273; hg19: chr10-111973339;