rs150652745
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_020774.4(MIB1):āc.3007A>Cā(p.Ile1003Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,134 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
MIB1
NM_020774.4 missense
NM_020774.4 missense
Scores
5
8
6
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.07
Genes affected
MIB1 (HGNC:21086): (MIB E3 ubiquitin protein ligase 1) This gene encodes a protein containing multiple ankyrin repeats and RING finger domains that functions as an E3 ubiquitin ligase. The encoded protein positively regulates Notch signaling by ubiquitinating the Notch receptors, thereby facilitating their endocytosis. This protein may also promote the ubiquitination and degradation of death-associated protein kinase 1 (DAPK1). [provided by RefSeq, Jun 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33338156).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MIB1 | NM_020774.4 | c.3007A>C | p.Ile1003Leu | missense_variant | 21/21 | ENST00000261537.7 | NP_065825.1 | |
MIB1 | XM_047437676.1 | c.2758A>C | p.Ile920Leu | missense_variant | 21/21 | XP_047293632.1 | ||
MIB1 | XM_011526098.2 | c.1537A>C | p.Ile513Leu | missense_variant | 12/12 | XP_011524400.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MIB1 | ENST00000261537.7 | c.3007A>C | p.Ile1003Leu | missense_variant | 21/21 | 1 | NM_020774.4 | ENSP00000261537.6 | ||
MIB1 | ENST00000578646.5 | n.2984A>C | non_coding_transcript_exon_variant | 21/21 | 2 | |||||
MIB1 | ENST00000695487.1 | n.1336A>C | non_coding_transcript_exon_variant | 4/4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251316Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135834
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461134Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 726900
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ExAC
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ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
B
Vest4
MutPred
Loss of MoRF binding (P = 0.0809);
MVP
MPC
ClinPred
D
GERP RS
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