chr14-36316749-C-T

Variant names:

• chr14-36316749-C-T
• rs1405500440
• NM_016586.3:c.193G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12339327).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBIP	NM_016586.3	MANE Select	c.193G>A	p.Ala65Thr	missense	Exon 2 of 9	NP_057670.2	Q9NS73-1
	MBIP	NM_001144891.2		c.193G>A	p.Ala65Thr	missense	Exon 2 of 9	NP_001138363.1	Q9NS73-5
	MBIP	NM_001308110.2		c.193G>A	p.Ala65Thr	missense	Exon 2 of 8	NP_001295039.1	Q9NS73-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBIP	ENST00000416007.9	TSL:1 MANE Select	c.193G>A	p.Ala65Thr	missense	Exon 2 of 9	ENSP00000399718.2	Q9NS73-1
	MBIP	ENST00000318473.11	TSL:1	c.193G>A	p.Ala65Thr	missense	Exon 2 of 9	ENSP00000324444.5	Q9NS73-5
	MBIP	ENST00000359527.11	TSL:1	c.193G>A	p.Ala65Thr	missense	Exon 2 of 8	ENSP00000352517.5	Q9NS73-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.075
Eigen_PC	Benign	-0.014
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.3
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.014
Sift	Benign	0.34	T
Sift4G	Benign	0.56	T
Polyphen		0.0030	B
Vest4		0.23
MutPred		0.26		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
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs1405500440; hg19: chr14-36785955; COSMIC: COSV100576777; COSMIC: COSV100576777;