Variant chr17-42568848-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198204.2(MLX):c.181A>G(p.Ser61Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000752 in 1,608,940 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 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000080 ( 0 hom. )

Consequence

MLX
NM_198204.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.06

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2044254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLX	NM_198204.2 link	c.181A>G	p.Ser61Gly	missense_variant	4/8	ENST00000435881.7	NP_937847.1	Q9UH92-3
MLX	NM_170607.3 link	c.343A>G	p.Ser115Gly	missense_variant	4/8		NP_733752.1	Q9UH92-1
MLX	NM_198205.2 link	c.91A>G	p.Ser31Gly	missense_variant	3/7		NP_937848.1	Q9UH92-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLX	ENST00000435881.7 link	c.181A>G	p.Ser61Gly	missense_variant	4/8	1	NM_198204.2	ENSP00000416627.1		Q9UH92-3

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

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:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000831

AC:

AN:

240808

Hom.:

AF XY:

0.000123

AC XY:

AN XY:

130334

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000271

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000922

Gnomad OTH exome

AF:

0.000336

GnomAD4 exome

AF:

0.0000796

AC:

116

AN:

1456630

Hom.:

Cov.:

AF XY:

0.0000953

AC XY:

AN XY:

724138

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000504

Gnomad4 FIN exome

AF:

0.000113

Gnomad4 NFE exome

AF:

0.0000505

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000947

Hom.:

Bravo

AF:

0.0000189

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000140

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

Aug 04, 2024

The c.343A>G (p.S115G) alteration is located in exon 4 (coding exon 4) of the MLX gene. This alteration results from a A to G substitution at nucleotide position 343, causing the serine (S) at amino acid position 115 to be replaced by a glycine (G). 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

Benign

-0.079

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.071

.;T;.;T

Eigen

Uncertain

0.65

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.97

D;D;D;D

M_CAP

Benign

0.053

MetaRNN

Benign

0.20

T;T;T;T

MetaSVM

Uncertain

0.090

MutationAssessor

Benign

0.69

.;N;.;.

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.6

N;N;N;.

REVEL

Uncertain

0.38

Sift

Uncertain

0.014

D;D;D;.

Sift4G

Benign

0.14

T;T;T;T

Polyphen

0.97

D;P;D;.

Vest4

0.58

MVP

0.89

MPC

0.97

ClinPred

0.17

GERP RS

5.5

Varity_R

0.37

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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