chr10-110207935-G-A

Variant names:

• chr10-110207935-G-A
• rs141964073
• NM_130439.3:c.127G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_130439.3(MXI1):​c.127G>A​(p.Ala43Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00264 in 1,559,600 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0027 (9 hom.)
• Consequence: MXI1 NM_130439.3 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 4.53
• Publications: 5 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008568615).
• BP6: Variant 10-110207935-G-A is Benign according to our data. Variant chr10-110207935-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3052445.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MXI1	NM_130439.3	c.127G>A	p.Ala43Thr	missense_variant	Exon 1 of 6	ENST00000332674.9	NP_569157.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MXI1	ENST00000332674.9	c.127G>A	p.Ala43Thr	missense_variant	Exon 1 of 6	1	NM_130439.3	ENSP00000331152.5
MXI1	ENST00000453116.5	c.127G>A	p.Ala43Thr	missense_variant	Exon 1 of 4	5		ENSP00000398981.1
ENSG00000228417	ENST00000451656.1	n.385C>T		non_coding_transcript_exon_variant	Exon 3 of 3	3
ENSG00000303571	ENST00000795696.1	n.-111C>T		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.00195 AC: 293 AN: 150560 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000703

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00165

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.000202

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00332

Gnomad OTH AF: 0.00241

GnomAD2 exomes AF: 0.00163 AC: 343 AN: 210358 AF XY: 0.00181

Gnomad AFR exome AF: 0.000355

Gnomad AMR exome AF: 0.000865

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000286

Gnomad NFE exome AF: 0.00279

Gnomad OTH exome AF: 0.00124

GnomAD4 exome AF: 0.00272 AC: 3832 AN: 1408930 Hom.: 9 Cov.: 32 AF XY: 0.00265 AC XY: 1854 AN XY: 700596

African (AFR) AF: 0.000605 AC: 18 AN: 29730

American (AMR) AF: 0.000973 AC: 38 AN: 39046

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24510

East Asian (EAS) AF: 0.00 AC: 0 AN: 33542

South Asian (SAS) AF: 0.00124 AC: 102 AN: 82062

European-Finnish (FIN) AF: 0.000484 AC: 25 AN: 51654

Middle Eastern (MID) AF: 0.000623 AC: 3 AN: 4818

European-Non Finnish (NFE) AF: 0.00323 AC: 3504 AN: 1085994

Other (OTH) AF: 0.00247 AC: 142 AN: 57574

GnomAD4 genome AF: 0.00194 AC: 293 AN: 150670 Hom.: 0 Cov.: 31 AF XY: 0.00166 AC XY: 122 AN XY: 73618

African (AFR) AF: 0.000701 AC: 29 AN: 41370

American (AMR) AF: 0.00165 AC: 25 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4824

European-Finnish (FIN) AF: 0.000202 AC: 2 AN: 9912

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00332 AC: 224 AN: 67510

Other (OTH) AF: 0.00238 AC: 5 AN: 2098

Alfa AF: 0.00191 Hom.: 7

Bravo AF: 0.00184

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00349 AC: 30

ExAC AF: 0.00164 AC: 199

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

MXI1-related disorder Benign:1

May 21, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Uncertain	0.99
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.70	T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.0086	T;T
MetaSVM	Benign	-1.0	T
PhyloP100		4.5
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.29	N;N
REVEL	Benign	0.088
Sift	Uncertain	0.0070	D;D
Sift4G	Benign	0.23	T;D
Polyphen		0.025	B;.
Vest4		0.20
MVP		0.18
MPC		0.55
ClinPred		0.061	T
GERP RS		2.5
PromoterAI		-0.0022	Neutral
gMVP		0.39
Mutation Taster		=93/7	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: rs141964073; hg19: chr10-111967693; COSMIC: COSV100221822; COSMIC: COSV100221822;