NM_016586.3:c.193G>A

Variant names:

• chr14-36316749-C-T
• NM_016586.3:c.193G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28

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]

ACMG classification

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
MBIP	NM_016586.3	c.193G>A	p.Ala65Thr	missense_variant	Exon 2 of 9	ENST00000416007.9	NP_057670.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBIP	ENST00000416007.9	c.193G>A	p.Ala65Thr	missense_variant	Exon 2 of 9	1	NM_016586.3	ENSP00000399718.2

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

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;