rs775387822

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The XM_047446594.1(MIB2):​c.11C>A​(p.Ala4Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000737 in 1,356,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

MIB2
XM_047446594.1 missense

Scores

1
1
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.534
Variant links:
Genes affected
MIB2 (HGNC:30577): (MIB E3 ubiquitin protein ligase 2) The protein encoded by this gene is an E3 ubiquitin protein ligase that mediates ubiquitination of proteins in the Notch signaling pathway. The encoded protein may be a suppressor of melanoma invasion. [provided by RefSeq, Mar 2017]

Genome browser will be placed here

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=0.11057359).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MIB2NM_001170687.4 linkc.-293C>A upstream_gene_variant ENST00000355826.10 NP_001164158.3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MIB2ENST00000355826.10 linkc.-293C>A upstream_gene_variant 1 NM_001170687.4 ENSP00000348081.6 Q96AX9-1E9PD12

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
7.37e-7
AC:
1
AN:
1356444
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
667702
show subpopulations
Gnomad4 AFR exome
AF:
0.0000343
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.11C>A (p.A4E) alteration is located in exon 1 (coding exon 1) of the MIB2 gene. This alteration results from a C to A substitution at nucleotide position 11, causing the alanine (A) at amino acid position 4 to be replaced by a glutamic acid (E). 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
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
3.9
DANN
Benign
0.66
Eigen
Benign
-0.76
Eigen_PC
Benign
-0.91
FATHMM_MKL
Benign
0.033
N
LIST_S2
Benign
0.30
T;T;T;T
M_CAP
Benign
0.042
D
MetaRNN
Benign
0.11
T;T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
0.040
N;N;N;N
REVEL
Benign
0.042
Sift
Pathogenic
0.0
D;D;D;D
Vest4
0.18
MutPred
0.33
Gain of solvent accessibility (P = 0.005);Gain of solvent accessibility (P = 0.005);Gain of solvent accessibility (P = 0.005);Gain of solvent accessibility (P = 0.005);
MVP
0.14
MPC
1.2
ClinPred
0.29
T
GERP RS
1.6
gMVP
0.075

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.

Other links and lift over

dbSNP: rs775387822; hg19: chr1-1550850; API