Variant chr17-42567129-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198204.2(MLX):c.5C>T(p.Thr2Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000452 in 1,106,970 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000045 ( 0 hom. )

Consequence

MLX
NM_198204.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.02

Variant links:

Genes affected

MLX (HGNC:11645): (MAX dimerization protein MLX) The product of this gene belongs to the family of basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factors. These factors form heterodimers with Mad proteins and play a role in proliferation, determination and differentiation. This gene product may act to diversify Mad family function by its restricted association with a subset of the Mad family of transcriptional repressors, namely, Mad1 and Mad4. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

MLX links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLX	NM_198204.2 link	c.5C>T	p.Thr2Met	missense_variant	1/8	ENST00000435881.7	NP_937847.1	Q9UH92-3
MLX	NM_170607.3 link	c.5C>T	p.Thr2Met	missense_variant	1/8		NP_733752.1	Q9UH92-1
MLX	NM_198205.2 link	c.5C>T	p.Thr2Met	missense_variant	1/7		NP_937848.1	Q9UH92-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLX	ENST00000435881.7 link	c.5C>T	p.Thr2Met	missense_variant	1/8	1	NM_198204.2	ENSP00000416627.1		Q9UH92-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000452

AC:

AN:

1106970

Hom.:

Cov.:

AF XY:

0.00000761

AC XY:

AN XY:

525656

show subpopulations

Gnomad4 AFR exome

AF:

0.0000428

Gnomad4 AMR exome

AF:

0.0000897

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000321

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2024

The c.5C>T (p.T2M) alteration is located in exon 1 (coding exon 1) of the MLX gene. This alteration results from a C to T substitution at nucleotide position 5, causing the threonine (T) at amino acid position 2 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Uncertain

0.061

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.045

.;T;.;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

T;T;T;T

M_CAP

Pathogenic

0.41

MetaRNN

Uncertain

0.56

D;D;D;D

MetaSVM

Uncertain

0.19

MutationAssessor

Benign

0.69

N;N;N;.

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.4

N;N;N;.

REVEL

Uncertain

0.34

Sift

Uncertain

0.0020

D;D;D;.

Sift4G

Uncertain

0.0070

D;D;D;D

Polyphen

1.0

D;D;D;.

Vest4

0.47

MutPred

0.14

Loss of phosphorylation at T2 (P = 0.0241);Loss of phosphorylation at T2 (P = 0.0241);Loss of phosphorylation at T2 (P = 0.0241);Loss of phosphorylation at T2 (P = 0.0241);

MVP

0.93

MPC

1.0

ClinPred

0.94

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.31

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over