Variant rs150652745 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000261537.7(MIB1):c.3007A>C(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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I1003V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MIB1
ENST00000261537.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.07

Variant links:

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]

MIB1 links:

Genome browser will be placed here

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
MIB1	NM_020774.4 linkuse as main transcript	c.3007A>C	p.Ile1003Leu	missense_variant	21/21	ENST00000261537.7	NP_065825.1
MIB1	XM_047437676.1 linkuse as main transcript	c.2758A>C	p.Ile920Leu	missense_variant	21/21		XP_047293632.1
MIB1	XM_011526098.2 linkuse as main transcript	c.1537A>C	p.Ile513Leu	missense_variant	12/12		XP_011524400.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MIB1	ENST00000261537.7 linkuse as main transcript	c.3007A>C	p.Ile1003Leu	missense_variant	21/21	1	NM_020774.4	ENSP00000261537	P1
MIB1	ENST00000578646.5 linkuse as main transcript	n.2984A>C		non_coding_transcript_exon_variant	21/21	2
MIB1	ENST00000695487.1 linkuse as main transcript	n.1336A>C		non_coding_transcript_exon_variant	4/4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251316

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461134

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726900

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.64

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.056

MetaRNN

Benign

0.33

MetaSVM

Uncertain

-0.20

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.3

REVEL

Uncertain

0.55

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.17

Vest4

0.57

MutPred

0.31

Loss of MoRF binding (P = 0.0809);

MVP

0.51

MPC

0.70

ClinPred

0.72

GERP RS

5.4

Varity_R

0.56

gMVP

0.57

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over