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GeneBe

7-73596166-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032951.3(MLXIPL):​c.2045A>C​(p.Gln682Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

MLXIPL
NM_032951.3 missense

Scores

5
10
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.26
Variant links:
Genes affected
MLXIPL (HGNC:12744): (MLX interacting protein like) This gene encodes a basic helix-loop-helix leucine zipper transcription factor of the Myc/Max/Mad superfamily. This protein forms a heterodimeric complex and binds and activates, in a glucose-dependent manner, carbohydrate response element (ChoRE) motifs in the promoters of triglyceride synthesis genes. The gene is deleted in Williams-Beuren syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at chromosome 7q11.23. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MLXIPLNM_032951.3 linkuse as main transcriptc.2045A>C p.Gln682Pro missense_variant 13/17 ENST00000313375.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MLXIPLENST00000313375.8 linkuse as main transcriptc.2045A>C p.Gln682Pro missense_variant 13/171 NM_032951.3 A2Q9NP71-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
35
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 28, 2024The c.2045A>C (p.Q682P) alteration is located in exon 13 (coding exon 13) of the MLXIPL gene. This alteration results from a A to C substitution at nucleotide position 2045, causing the glutamine (Q) at amino acid position 682 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Pathogenic
0.32
D
BayesDel_noAF
Pathogenic
0.23
CADD
Pathogenic
29
DANN
Uncertain
0.99
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.91
D;D;D;D;D
M_CAP
Uncertain
0.20
D
MetaRNN
Uncertain
0.64
D;D;D;D;D
MetaSVM
Pathogenic
1.1
D
MutationTaster
Benign
1.0
D;D;D;D;D;D
PrimateAI
Uncertain
0.64
T
PROVEAN
Uncertain
-2.9
D;D;D;D;D
REVEL
Pathogenic
0.81
Sift
Uncertain
0.012
D;D;D;D;D
Sift4G
Uncertain
0.043
D;D;D;D;T
Polyphen
0.11
B;D;D;B;.
Vest4
0.76
MutPred
0.41
.;Gain of glycosylation at Q682 (P = 0.0138);Gain of glycosylation at Q682 (P = 0.0138);.;.;
MVP
0.63
MPC
0.51
ClinPred
0.96
D
GERP RS
5.4
Varity_R
0.64
gMVP
0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-73010496; API