17-42568473-T-C

Variant names:

• chr17-42568473-T-C
• NM_198204.2:c.83T>C

Variant summary

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

The NM_198204.2(MLX):​c.83T>C​(p.Leu28Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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)
• Consequence: MLX NM_198204.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.70

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=0.22080213).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLX	NM_198204.2	c.83T>C	p.Leu28Pro	missense_variant	Exon 3 of 8	ENST00000435881.7	NP_937847.1
MLX	NM_170607.3	c.245T>C	p.Leu82Pro	missense_variant	Exon 3 of 8		NP_733752.1
MLX	NM_198205.2	c.80-364T>C		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.83T>C	p.Leu28Pro	missense_variant	Exon 3 of 8	1	NM_198204.2	ENSP00000416627.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	.;T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.081
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.55	.;N
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.010	N;N
REVEL	Benign	0.23
Sift	Uncertain	0.011	D;D
Sift4G	Benign	0.20	T;T
Polyphen		0.0020	B;B
Vest4		0.44
MutPred		0.33		.;Loss of stability (P = 0.0161);
MVP		0.89
MPC		1.0
ClinPred		0.88	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr17-40720491;