rs7953704

Positions:

• chr12-122141445-A-G

Variant summary

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

The NM_014938.6(MLXIP):​c.2639-246A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 152,084 control chromosomes in the GnomAD database, including 23,745 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 0.56 (23745 hom., cov: 32)
• Consequence: MLXIP NM_014938.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MLXIP	NM_014938.6	c.2639-246A>G		intron_variant		ENST00000319080.12
MLXIP	XM_006719290.5	c.2679A>G	p.Pro893=	synonymous_variant	17/18
MLXIP	XM_006719291.5	c.2676A>G	p.Pro892=	synonymous_variant	17/18
MLXIP	XM_006719292.5	c.2642-246A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MLXIP	ENST00000319080.12	c.2639-246A>G		intron_variant		1	NM_014938.6	P1
MLXIP	ENST00000538698.5	c.1460-246A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84444 AN: 151966 Hom.: 23732 Cov.: 32

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.556 AC: 84504 AN: 152084 Hom.: 23745 Cov.: 32 AF XY: 0.557 AC XY: 41384 AN XY: 74338

Gnomad4 AFR AF: 0.601

Gnomad4 AMR AF: 0.595

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.511

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.597

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.536

Alfa AF: 0.544 Hom.: 4756

Bravo AF: 0.556

Asia WGS AF: 0.527 AC: 1834 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	0.14
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs7953704; hg19: chr12-122625992;