Genetic Variant MLX:p.Ser61Gly (chr17-42568848-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_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

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198204.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MLX	NM_198204.2	MANE Select	c.181A>G	p.Ser61Gly	missense	Exon 4 of 8	NP_937847.1	Q9UH92-3
MLX	NM_170607.3		c.343A>G	p.Ser115Gly	missense	Exon 4 of 8	NP_733752.1	Q9UH92-1
MLX	NM_198205.2		c.91A>G	p.Ser31Gly	missense	Exon 3 of 7	NP_937848.1	Q9UH92-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MLX	ENST00000435881.7	TSL:1 MANE Select	c.181A>G	p.Ser61Gly	missense	Exon 4 of 8	ENSP00000416627.1	Q9UH92-3
MLX	ENST00000246912.8	TSL:1	c.343A>G	p.Ser115Gly	missense	Exon 4 of 8	ENSP00000246912.3	Q9UH92-1
MLX	ENST00000346833.8	TSL:1	c.91A>G	p.Ser31Gly	missense	Exon 3 of 7	ENSP00000320913.3	Q9UH92-2

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

GnomAD2 exomes

AF:

0.0000831

AC:

AN:

240808

AF XY:

0.000123

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 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

African (AFR)

AF:

0.00

AC:

AN:

33326

American (AMR)

AF:

0.00

AC:

AN:

44096

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25978

East Asian (EAS)

AF:

0.00

AC:

AN:

39564

South Asian (SAS)

AF:

0.000504

AC:

AN:

85366

European-Finnish (FIN)

AF:

0.000113

AC:

AN:

53012

Middle Eastern (MID)

AF:

0.000694

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000505

AC:

AN:

1109350

Other (OTH)

AF:

0.000116

AC:

AN:

60172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41566

American (AMR)

AF:

0.00

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.071

Eigen

Uncertain

0.65

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.97

M_CAP

Benign

0.053

MetaRNN

Benign

0.20

MetaSVM

Uncertain

0.090

MutationAssessor

Benign

0.69

PhyloP100

7.1

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.6

REVEL

Uncertain

0.38

Sift

Uncertain

0.014

Sift4G

Benign

0.14

Polyphen

0.97

Vest4

0.58

MVP

0.89

MPC

0.97

ClinPred

0.17

GERP RS

5.5

Varity_R

0.37

gMVP

0.30

Mutation Taster

=34/66

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over