Variant 1-1623402-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_080875.5(MIB2):c.-51C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000388 in 1,599,816 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00040 ( 3 hom. )

Consequence

MIB2
NM_080875.5 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.40

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]

MIB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012884736).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIB2	NM_001170687.4 link	c.-22-29C>T		intron_variant	Intron 2 of 19	ENST00000355826.10	NP_001164158.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIB2	ENST00000355826.10 link	c.-22-29C>T		intron_variant	Intron 2 of 19	1	NM_001170687.4	ENSP00000348081.6		Q96AX9-1E9PD12

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000460

AC:

101

AN:

219350

Hom.:

AF XY:

0.000512

AC XY:

AN XY:

121122

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000544

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00156

Gnomad FIN exome

AF:

0.0000524

Gnomad NFE exome

AF:

0.000370

Gnomad OTH exome

AF:

0.000374

GnomAD4 exome

AF:

0.000399

AC:

577

AN:

1447602

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

328

AN XY:

719706

show subpopulations

Gnomad4 AFR exome

AF:

0.0000613

Gnomad4 AMR exome

AF:

0.000618

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.00157

Gnomad4 FIN exome

AF:

0.0000196

Gnomad4 NFE exome

AF:

0.000346

Gnomad4 OTH exome

AF:

0.000403

GnomAD4 genome

AF:

0.000282

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000437

Hom.:

Bravo

AF:

0.000325

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000487

AC:

ExAC

AF:

0.000444

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 18, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.295C>T (p.R99W) alteration is located in exon 3 (coding exon 3) of the MIB2 gene. This alteration results from a C to T substitution at nucleotide position 295, causing the arginine (R) at amino acid position 99 to be replaced by a tryptophan (W). 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

-0.52

BayesDel_noAF

Benign

-0.55

CADD

Benign

3.9

DANN

Benign

0.97

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.60

T;T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.013

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.72

N;N;N

REVEL

Benign

0.081

Sift

Benign

0.071

T;D;T

Sift4G

Uncertain

0.0030

D;D;D

Vest4

0.090

MVP

0.43

MPC

0.71

ClinPred

0.098

GERP RS

0.14

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over