10-110213581-C-T

Position:

• chr10-110213581-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MXI1	NM_130439.3	c.274+5499C>T		intron_variant		ENST00000332674.9
LOC105378480	XR_946315.4	n.8025G>A		non_coding_transcript_exon_variant	2/2
MXI1	NM_001008541.1	c.-36+3266C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MXI1	ENST00000332674.9	c.274+5499C>T		intron_variant		1	NM_130439.3
MXI1	ENST00000361248.8	c.-36+3266C>T		intron_variant		1
MXI1	ENST00000453116.5	c.274+5499C>T		intron_variant		5

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

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.0823

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.242

Alfa AF: 0.179 Hom.: 2593

Bravo AF: 0.264

Asia WGS AF: 0.190 AC: 662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.1
DANN	Benign	0.69

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: rs1342273; hg19: chr10-111973339;