chr7-73596650-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_032951.3(MLXIPL):āc.1811C>Gā(p.Pro604Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000094 in 1,595,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000072 ( 0 hom., cov: 31)
Exomes š: 0.0000028 ( 0 hom. )
Consequence
MLXIPL
NM_032951.3 missense
NM_032951.3 missense
Scores
5
13
Clinical Significance
Conservation
PhyloP100: 6.49
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.23231852).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MLXIPL | NM_032951.3 | c.1811C>G | p.Pro604Arg | missense_variant | 11/17 | ENST00000313375.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MLXIPL | ENST00000313375.8 | c.1811C>G | p.Pro604Arg | missense_variant | 11/17 | 1 | NM_032951.3 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152152Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00000451 AC: 1AN: 221752Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 121118
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GnomAD4 exome AF: 0.00000277 AC: 4AN: 1443646Hom.: 0 Cov.: 34 AF XY: 0.00000140 AC XY: 1AN XY: 716082
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GnomAD4 genome AF: 0.0000723 AC: 11AN: 152152Hom.: 0 Cov.: 31 AF XY: 0.0000673 AC XY: 5AN XY: 74326
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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 submitter | clinical testing | Ambry Genetics | Oct 22, 2021 | The c.1811C>G (p.P604R) alteration is located in exon 11 (coding exon 11) of the MLXIPL gene. This alteration results from a C to G substitution at nucleotide position 1811, causing the proline (P) at amino acid position 604 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;M;.
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Benign
Sift
Benign
D;D;D;D;D
Sift4G
Benign
T;T;T;T;T
Polyphen
D;D;D;D;.
Vest4
MutPred
Gain of MoRF binding (P = 5e-04);Gain of MoRF binding (P = 5e-04);Gain of MoRF binding (P = 5e-04);Gain of MoRF binding (P = 5e-04);.;
MVP
MPC
0.45
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at