1-1615497-C-G

Variant summary

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

The XM_047446594.1(MIB2):ā€‹c.38C>Gā€‹(p.Ser13Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,204 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 34)

Consequence

MIB2
XM_047446594.1 missense

Scores

1
1
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.01
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=0.087406754).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MIB2NM_001170687.4 linkc.-266C>G upstream_gene_variant ENST00000355826.10 NP_001164158.3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MIB2ENST00000355826.10 linkc.-266C>G upstream_gene_variant 1 NM_001170687.4 ENSP00000348081.6 Q96AX9-1E9PD12

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152204
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
32
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152204
Hom.:
0
Cov.:
34
AF XY:
0.0000134
AC XY:
1
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
1.4
DANN
Benign
0.88
Eigen
Benign
-0.81
Eigen_PC
Benign
-0.95
FATHMM_MKL
Benign
0.027
N
LIST_S2
Benign
0.39
T;T;T;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.087
T;T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-0.35
N;N;N;N
REVEL
Benign
0.035
Sift
Benign
0.042
D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D
Vest4
0.078
MutPred
0.18
Loss of phosphorylation at S13 (P = 0.0068);Loss of phosphorylation at S13 (P = 0.0068);Loss of phosphorylation at S13 (P = 0.0068);Loss of phosphorylation at S13 (P = 0.0068);
MVP
0.14
MPC
0.43
ClinPred
0.22
T
GERP RS
1.7
gMVP
0.072

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: rs1046631657; hg19: chr1-1550877; API