NM_198204.2:c.100C>A

Variant names:

• chr17-42568490-C-A
• NM_198204.2:c.100C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198204.2(MLX):​c.100C>A​(p.Arg34Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MLX NM_198204.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.928

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

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=0.15890703).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLX	NM_198204.2	c.100C>A	p.Arg34Ser	missense_variant	Exon 3 of 8	ENST00000435881.7	NP_937847.1
MLX	NM_170607.3	c.262C>A	p.Arg88Ser	missense_variant	Exon 3 of 8		NP_733752.1
MLX	NM_198205.2	c.80-347C>A		intron_variant	Intron 2 of 6		NP_937848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLX	ENST00000435881.7	c.100C>A	p.Arg34Ser	missense_variant	Exon 3 of 8	1	NM_198204.2	ENSP00000416627.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461620 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727120

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	.;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.55	.;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.090	N;N
REVEL	Benign	0.15
Sift	Benign	0.068	T;T
Sift4G	Benign	0.69	T;T
Polyphen		0.052	B;B
Vest4		0.32
MutPred		0.26		.;Loss of MoRF binding (P = 0.0236);
MVP		0.89
MPC		0.54
ClinPred		0.68	D
GERP RS		4.3
Varity_R		0.34
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-40720508;