dbSNP rs1880845422: MBIP:p.Ser11Ile (chr14-36320557-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016586.3(MBIP):c.32G>T(p.Ser11Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. S11N) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MBIP
NM_016586.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.704

Publications

0 publications found

Variant links:

Genes affected

MBIP (HGNC:20427): (MAP3K12 binding inhibitory protein 1) Enables identical protein binding activity and protein kinase inhibitor activity. Involved in histone H3 acetylation; positive regulation of JNK cascade; and positive regulation of gene expression. Located in cytosol; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MBIP links:

ENSG00000283098 (HGNC:):

ENSG00000283098 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055814236).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016586.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MBIP	NM_016586.3	MANE Select	c.32G>T	p.Ser11Ile	missense	Exon 1 of 9	NP_057670.2	Q9NS73-1
MBIP	NM_001144891.2		c.32G>T	p.Ser11Ile	missense	Exon 1 of 9	NP_001138363.1	Q9NS73-5
MBIP	NM_001308110.2		c.32G>T	p.Ser11Ile	missense	Exon 1 of 8	NP_001295039.1	Q9NS73-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MBIP	ENST00000416007.9	TSL:1 MANE Select	c.32G>T	p.Ser11Ile	missense	Exon 1 of 9	ENSP00000399718.2	Q9NS73-1
MBIP	ENST00000318473.11	TSL:1	c.32G>T	p.Ser11Ile	missense	Exon 1 of 9	ENSP00000324444.5	Q9NS73-5
MBIP	ENST00000359527.11	TSL:1	c.32G>T	p.Ser11Ile	missense	Exon 1 of 8	ENSP00000352517.5	Q9NS73-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461156

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726886

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33458

American (AMR)

AF:

0.00

AC:

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26092

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.00

AC:

AN:

86196

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53296

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111672

Other (OTH)

AF:

0.00

AC:

AN:

60354

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

1.4

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.024

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.76

M_CAP

Benign

0.0090

MetaRNN

Benign

0.056

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

-0.70

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.0

REVEL

Benign

0.049

Sift

Uncertain

0.010

Sift4G

Uncertain

0.047

Polyphen

0.032

Vest4

0.19

MutPred

0.20

Gain of catalytic residue at S11 (P = 0.0075)

MVP

0.21

MPC

0.11

ClinPred

0.18

GERP RS

-4.2

PromoterAI

0.045

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.081

gMVP

0.30

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over