rs2010750

Variant names:

• chr17-42571373-C-T
• rs2010750
• NM_198204.2:c.679-174C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198204.2(MLX):​c.679-174C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 151,968 control chromosomes in the GnomAD database, including 10,397 homozygotes. 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: 𝑓 0.36 (10397 hom., cov: 32)
• Consequence: MLX NM_198204.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.929
• Publications: 14 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLX	NM_198204.2	c.679-174C>T		intron_variant	Intron 7 of 7	ENST00000435881.7	NP_937847.1
MLX	NM_170607.3	c.841-174C>T		intron_variant	Intron 7 of 7		NP_733752.1
MLX	NM_198205.2	c.589-174C>T		intron_variant	Intron 6 of 6		NP_937848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLX	ENST00000435881.7	c.679-174C>T		intron_variant	Intron 7 of 7	1	NM_198204.2	ENSP00000416627.1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54110 AN: 151850 Hom.: 10401 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.397

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.356 AC: 54124 AN: 151968 Hom.: 10397 Cov.: 32 AF XY: 0.359 AC XY: 26649 AN XY: 74276

African (AFR) AF: 0.212 AC: 8785 AN: 41450

American (AMR) AF: 0.446 AC: 6806 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1897 AN: 3464

East Asian (EAS) AF: 0.540 AC: 2785 AN: 5158

South Asian (SAS) AF: 0.323 AC: 1556 AN: 4820

European-Finnish (FIN) AF: 0.367 AC: 3880 AN: 10558

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 27021 AN: 67932

Other (OTH) AF: 0.395 AC: 832 AN: 2108

Alfa AF: 0.374 Hom.: 1481

Bravo AF: 0.357

Asia WGS AF: 0.367 AC: 1273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.57
DANN	Benign	0.59
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism (auto)

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: rs2010750; hg19: chr17-40723391; COSMIC: COSV53819372; COSMIC: COSV53819372;