NM_198204.2:c.92A>G

Variant names:

• chr17-42568482-A-G
• rs769122835
• NM_198204.2:c.92A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_198204.2(MLX):​c.92A>G​(p.Glu31Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,461,586 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: not found (cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: MLX NM_198204.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.69
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35117173).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLX	NM_198204.2	MANE Select	c.92A>G	p.Glu31Gly	missense	Exon 3 of 8	NP_937847.1	Q9UH92-3
	MLX	NM_170607.3		c.254A>G	p.Glu85Gly	missense	Exon 3 of 8	NP_733752.1	Q9UH92-1
	MLX	NM_198205.2		c.80-355A>G		intron	N/A	NP_937848.1	Q9UH92-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLX	ENST00000435881.7	TSL:1 MANE Select	c.92A>G	p.Glu31Gly	missense	Exon 3 of 8	ENSP00000416627.1	Q9UH92-3
	MLX	ENST00000246912.8	TSL:1	c.254A>G	p.Glu85Gly	missense	Exon 3 of 8	ENSP00000246912.3	Q9UH92-1
	MLX	ENST00000346833.8	TSL:1	c.80-355A>G		intron	N/A	ENSP00000320913.3	Q9UH92-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251390 AF XY: 0.0000147

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: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000171 AC: 25 AN: 1461586 Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14 AN XY: 727116

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000198 AC: 22 AN: 1111830

Other (OTH) AF: 0.0000497 AC: 3 AN: 60376

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.081	T
Eigen	Benign	0.079
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	0.55	N
PhyloP100		8.7
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.36
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.015	D
Polyphen		0.22	B
Vest4		0.62
MutPred		0.22		Gain of MoRF binding (P = 0.0523)
MVP		0.89
MPC		0.62
ClinPred		0.63	D
GERP RS		5.3
Varity_R		0.39
gMVP		0.39
Mutation Taster		=11/89	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs769122835; hg19: chr17-40720500;