rs755439287

Variant names:

• chr17-42567251-C-A
• rs755439287
• ENST00000246912.8:c.127C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-42567251-C-A
• chr17-42567251-C-G
• chr17-42567251-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_170607.3(MLX):​c.127C>A​(p.Leu43Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000845 in 1,184,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L43F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.4e-7 (0 hom.)
• Consequence: MLX NM_170607.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.286
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.090953946).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170607.3. 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.42+85C>A		intron	N/A	NP_937847.1	Q9UH92-3
	MLX	NM_170607.3		c.127C>A	p.Leu43Ile	missense	Exon 1 of 8	NP_733752.1	Q9UH92-1
	MLX	NM_198205.2		c.42+85C>A		intron	N/A	NP_937848.1	Q9UH92-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLX	ENST00000246912.8	TSL:1	c.127C>A	p.Leu43Ile	missense	Exon 1 of 8	ENSP00000246912.3	Q9UH92-1
	MLX	ENST00000435881.7	TSL:1 MANE Select	c.42+85C>A		intron	N/A	ENSP00000416627.1	Q9UH92-3
	MLX	ENST00000346833.8	TSL:1	c.42+85C>A		intron	N/A	ENSP00000320913.3	Q9UH92-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.45e-7 AC: 1 AN: 1184004 Hom.: 0 Cov.: 31 AF XY: 0.00000176 AC XY: 1 AN XY: 566656

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25296

American (AMR) AF: 0.00 AC: 0 AN: 13440

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16114

East Asian (EAS) AF: 0.00 AC: 0 AN: 29760

South Asian (SAS) AF: 0.00 AC: 0 AN: 39382

European-Finnish (FIN) AF: 0.0000255 AC: 1 AN: 39200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3478

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 969180

Other (OTH) AF: 0.00 AC: 0 AN: 48154

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	9.8
DANN	Benign	0.93
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.44	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.29
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.086
Sift	Benign	0.21	T
Sift4G	Benign	0.33	T
Polyphen		0.014	B
Vest4		0.22
MutPred		0.30		Gain of sheet (P = 0.0266)
MVP		0.59
MPC		0.32
ClinPred		0.12	T
GERP RS		1.9
PromoterAI		0.074	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.049
gMVP		0.11

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

Other links and lift over

dbSNP: rs755439287; hg19: chr17-40719269;