10-110207915-C-T

Variant names:

• chr10-110207915-C-T
• rs1854402737
• NM_130439.3:c.107C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_130439.3(MXI1):​c.107C>T​(p.Pro36Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000666 in 150,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P36R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MXI1 NM_130439.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13
• Publications: 0 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]

ENSG00000228417 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1736772).

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.107C>T	p.Pro36Leu	missense	Exon 1 of 6	NP_569157.2	P50539-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MXI1	ENST00000332674.9	TSL:1 MANE Select	c.107C>T	p.Pro36Leu	missense	Exon 1 of 6	ENSP00000331152.5	P50539-3
	MXI1	ENST00000453116.5	TSL:5	c.107C>T	p.Pro36Leu	missense	Exon 1 of 4	ENSP00000398981.1	F6U3F6
	ENSG00000228417	ENST00000451656.1	TSL:3	n.405G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.00000666 AC: 1 AN: 150190 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1370780 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 680334

African (AFR) AF: 0.00 AC: 0 AN: 28042

American (AMR) AF: 0.00 AC: 0 AN: 33550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23504

East Asian (EAS) AF: 0.00 AC: 0 AN: 30452

South Asian (SAS) AF: 0.00 AC: 0 AN: 78378

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49734

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4216

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1067240

Other (OTH) AF: 0.00 AC: 0 AN: 55664

GnomAD4 genome AF: 0.00000666 AC: 1 AN: 150190 Hom.: 0 Cov.: 31 AF XY: 0.0000136 AC XY: 1 AN XY: 73338

African (AFR) AF: 0.00 AC: 0 AN: 41256

American (AMR) AF: 0.00 AC: 0 AN: 15100

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3444

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9760

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67330

Other (OTH) AF: 0.00 AC: 0 AN: 2072

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	22
DANN	Uncertain	0.99
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.1
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.090
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.18	T
Polyphen		0.0	B
Vest4		0.21
MVP		0.12
MPC		0.58
ClinPred		0.98	D
GERP RS		3.1
PromoterAI		-0.026	Neutral
gMVP		0.31
Mutation Taster		=92/8	polymorphism

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: rs1854402737; hg19: chr10-111967673;