Variant 17-42567146-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_198204.2(MLX):c.22C>A(p.Pro8Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000253 in 1,267,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000081 ( 0 hom. )

Consequence

MLX
NM_198204.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.31

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31943345).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MLX	NM_198204.2 linkuse as main transcript	c.22C>A	p.Pro8Thr	missense_variant	1/8	ENST00000435881.7
MLX	NM_170607.3 linkuse as main transcript	c.22C>A	p.Pro8Thr	missense_variant	1/8
MLX	NM_198205.2 linkuse as main transcript	c.22C>A	p.Pro8Thr	missense_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MLX	ENST00000435881.7 linkuse as main transcript	c.22C>A	p.Pro8Thr	missense_variant	1/8	1	NM_198204.2	P1	Q9UH92-3

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000807

AC:

AN:

1114886

Hom.:

Cov.:

AF XY:

0.0000113

AC XY:

AN XY:

530078

show subpopulations

Gnomad4 AFR exome

AF:

0.000297

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.0000444

GnomAD4 genome

AF:

0.000151

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.000482

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000230

ExAC

AF:

0.00000967

AC:

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

Dec 13, 2023

The c.22C>A (p.P8T) alteration is located in exon 1 (coding exon 1) of the MLX gene. This alteration results from a C to A substitution at nucleotide position 22, causing the proline (P) at amino acid position 8 to be replaced by a threonine (T). 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

0.078

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.047

.;T;.;T

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.81

T;T;T;T

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.32

T;T;T;T

MetaSVM

Uncertain

0.065

MutationAssessor

Benign

0.69

N;N;N;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.3

N;N;N;.

REVEL

Uncertain

0.31

Sift

Uncertain

0.010

D;D;T;.

Sift4G

Uncertain

0.022

D;D;T;T

Polyphen

0.59

P;P;D;.

Vest4

0.41

MutPred

0.13

Gain of phosphorylation at P8 (P = 0.0207);Gain of phosphorylation at P8 (P = 0.0207);Gain of phosphorylation at P8 (P = 0.0207);Gain of phosphorylation at P8 (P = 0.0207);

MVP

0.94

MPC

0.46

ClinPred

0.89

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.55

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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