NM_016586.3:c.193G>A

Variant summary

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

The NM_016586.3(MBIP):​c.193G>A​(p.Ala65Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

MBIP
NM_016586.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.28
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]

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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=0.12339327).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MBIPNM_016586.3 linkc.193G>A p.Ala65Thr missense_variant Exon 2 of 9 ENST00000416007.9 NP_057670.2 Q9NS73-1B2RCV0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MBIPENST00000416007.9 linkc.193G>A p.Ala65Thr missense_variant Exon 2 of 9 1 NM_016586.3 ENSP00000399718.2 Q9NS73-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 12, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.193G>A (p.A65T) alteration is located in exon 2 (coding exon 2) of the MBIP gene. This alteration results from a G to A substitution at nucleotide position 193, causing the alanine (A) at amino acid position 65 to be replaced by a threonine (T). 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
AlphaMissense
Benign
0.074
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.021
T;T;.;.;T;T
Eigen
Benign
-0.075
Eigen_PC
Benign
-0.014
FATHMM_MKL
Benign
0.67
D
LIST_S2
Benign
0.79
T;T;T;T;T;T
M_CAP
Benign
0.0083
T
MetaRNN
Benign
0.12
T;T;T;T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
1.6
L;.;L;L;.;.
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-0.51
N;.;N;N;.;.
REVEL
Benign
0.014
Sift
Benign
0.34
T;.;T;T;.;.
Sift4G
Benign
0.56
T;T;T;T;.;.
Polyphen
0.0030
B;.;B;B;.;.
Vest4
0.23
MutPred
0.26
Gain of solvent accessibility (P = 0.1154);Gain of solvent accessibility (P = 0.1154);Gain of solvent accessibility (P = 0.1154);Gain of solvent accessibility (P = 0.1154);Gain of solvent accessibility (P = 0.1154);.;
MVP
0.65
MPC
0.079
ClinPred
0.14
T
GERP RS
3.3
Varity_R
0.043
gMVP
0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-36785955; COSMIC: COSV100576777; COSMIC: COSV100576777; API