chr17-42567251-C-T

Variant names:

• chr17-42567251-C-T
• rs755439287
• ENST00000246912.8:c.127C>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>T​(p.Leu43Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,336,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: MLX NM_170607.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.07236439).

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>T		intron	N/A	NP_937847.1	Q9UH92-3
	MLX	NM_170607.3		c.127C>T	p.Leu43Phe	missense	Exon 1 of 8	NP_733752.1	Q9UH92-1
	MLX	NM_198205.2		c.42+85C>T		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>T	p.Leu43Phe	missense	Exon 1 of 8	ENSP00000246912.3	Q9UH92-1
	MLX	ENST00000435881.7	TSL:1 MANE Select	c.42+85C>T		intron	N/A	ENSP00000416627.1	Q9UH92-3
	MLX	ENST00000346833.8	TSL:1	c.42+85C>T		intron	N/A	ENSP00000320913.3	Q9UH92-2

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152224 Hom.: 0 Cov.: 33

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000211 AC: 1 AN: 47424 AF XY: 0.00

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: 0.0000489

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000127 AC: 15 AN: 1184004 Hom.: 0 Cov.: 31 AF XY: 0.0000212 AC XY: 12 AN XY: 566656

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

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

Ashkenazi Jewish (ASJ) AF: 0.0000621 AC: 1 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: 0.00 AC: 0 AN: 39200

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

European-Non Finnish (NFE) AF: 0.0000144 AC: 14 AN: 969180

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

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152224 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74368

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000206 AC: 2

ClinVar

ClinVar submissions as Germline

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	0.062
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.43	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.29
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.13
Sift	Benign	0.11	T
Sift4G	Benign	0.18	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.32		Gain of sheet (P = 0.0125)
MVP		0.89
MPC		0.32
ClinPred		0.12	T
GERP RS		1.9
PromoterAI		0.23	Neutral
Varity_R		0.046
gMVP		0.21

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;