Genetic Variant MBIP:p.Ser11Asn (chr14-36320557-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_016586.3(MBIP):c.32G>A(p.Ser11Asn) 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 1,461,160 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. Variant has been reported in ClinVar 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

Likely benign criteria provided, single submitter B:1

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.052559525).

BP6

Variant 14-36320557-C-T is Benign according to our data. Variant chr14-36320557-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3124070.Status of the report is criteria_provided_single_submitter, 1 stars.

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>A	p.Ser11Asn	missense	Exon 1 of 9	NP_057670.2	Q9NS73-1
MBIP	NM_001144891.2		c.32G>A	p.Ser11Asn	missense	Exon 1 of 9	NP_001138363.1	Q9NS73-5
MBIP	NM_001308110.2		c.32G>A	p.Ser11Asn	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>A	p.Ser11Asn	missense	Exon 1 of 9	ENSP00000399718.2	Q9NS73-1
MBIP	ENST00000318473.11	TSL:1	c.32G>A	p.Ser11Asn	missense	Exon 1 of 9	ENSP00000324444.5	Q9NS73-5
MBIP	ENST00000359527.11	TSL:1	c.32G>A	p.Ser11Asn	missense	Exon 1 of 8	ENSP00000352517.5	Q9NS73-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461160

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726888

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33458

American (AMR)

AF:

0.00

AC:

AN:

44684

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:

0.00

AC:

AN:

53296

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111674

Other (OTH)

AF:

0.00

AC:

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.34

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.013

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.55

M_CAP

Benign

0.0053

MetaRNN

Benign

0.053

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.26

PhyloP100

-0.70

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.68

REVEL

Benign

0.034

Sift

Benign

0.26

Sift4G

Benign

0.13

Polyphen

0.0

Vest4

0.084

MutPred

0.11

Loss of phosphorylation at S11 (P = 0.037)

MVP

0.42

MPC

0.075

ClinPred

0.12

GERP RS

-4.2

PromoterAI

0.0037

Neutral

(source)

Varity_R

0.072

gMVP

0.13

Mutation Taster

=98/2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over