rs1043763

Positions:

• chr12-122146362-G-A
• chr12-122146362-G-C
• chr12-122146362-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014938.6(MLXIP):​c.*4550G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 151,606 control chromosomes in the GnomAD database, including 39,557 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 0.72 (39504 hom., cov: 30)
  • Exomes 𝑓: 0.73 (53 hom.)
• Consequence: MLXIP NM_014938.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.298

Genes affected

MLXIP (HGNC:17055): (MLX interacting protein) This gene encodes a protein that functions as part of a heterodimer to activate transcription. The encoded protein forms a heterodimer with Max-like protein X (MLX) and is involved in the regulation of genes in response to cellular glucose levels. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLXIP	NM_014938.6	c.*4550G>A		3_prime_UTR_variant	17/17	ENST00000319080.12	NP_055753.3
MLXIP	XM_006719290.5	c.*4542G>A		3_prime_UTR_variant	18/18		XP_006719353.1
MLXIP	XM_006719291.5	c.*4542G>A		3_prime_UTR_variant	18/18		XP_006719354.1
MLXIP	XM_006719292.5	c.*4550G>A		3_prime_UTR_variant	17/17		XP_006719355.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLXIP	ENST00000319080.12	c.*4550G>A		3_prime_UTR_variant	17/17	1	NM_014938.6	ENSP00000312834.6

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108276 AN: 151290 Hom.: 39485 Cov.: 30

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.790

Gnomad OTH AF: 0.739

GnomAD4 exome AF: 0.732 AC: 145 AN: 198 Hom.: 53 Cov.: 0 AF XY: 0.721 AC XY: 101 AN XY: 140

Gnomad4 AFR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.778

Gnomad4 NFE exome AF: 0.725

Gnomad4 OTH exome AF: 0.563

GnomAD4 genome AF: 0.716 AC: 108347 AN: 151408 Hom.: 39504 Cov.: 30 AF XY: 0.714 AC XY: 52823 AN XY: 73950

Gnomad4 AFR AF: 0.573

Gnomad4 AMR AF: 0.754

Gnomad4 ASJ AF: 0.920

Gnomad4 EAS AF: 0.580

Gnomad4 SAS AF: 0.761

Gnomad4 FIN AF: 0.702

Gnomad4 NFE AF: 0.790

Gnomad4 OTH AF: 0.738

Alfa AF: 0.790 Hom.: 47435

Bravo AF: 0.712

Asia WGS AF: 0.639 AC: 2223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1043763; hg19: chr12-122630909;