rs2010750

chr17-42571373-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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/exons	MANE	UniProt
MLX	NM_198204.2	c.679-174C>T		intron_variant		ENST00000435881.7
MLX	NM_170607.3	c.841-174C>T		intron_variant
MLX	NM_198205.2	c.589-174C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MLX	ENST00000435881.7	c.679-174C>T		intron_variant		1	NM_198204.2	P1

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

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.540

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.395

Alfa AF: 0.381 Hom.: 1468

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

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

LitVar

Other links and lift over

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