10-110208026-T-C

Variant names:

• chr10-110208026-T-C
• NM_130439.3:c.218T>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_130439.3(MXI1):​c.218T>C​(p.Val73Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MXI1 NM_130439.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.77
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3945037).

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.218T>C	p.Val73Ala	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.218T>C	p.Val73Ala	missense	Exon 1 of 6	ENSP00000331152.5	P50539-3
	MXI1	ENST00000453116.5	TSL:5	c.218T>C	p.Val73Ala	missense	Exon 1 of 4	ENSP00000398981.1	F6U3F6
	ENSG00000228417	ENST00000451656.1	TSL:3	n.294A>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	27
DANN	Uncertain	1.0
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.72	T
PhyloP100		5.8
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.22
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.83	P
Vest4		0.59
MutPred		0.38		Gain of disorder (P = 0.0679)
MVP		0.44
MPC		1.5
ClinPred		0.97	D
GERP RS		4.7
PromoterAI		0.044	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.64
Mutation Taster		=56/44	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

hg19: chr10-111967784;