14-36314710-A-T

Variant names:

• chr14-36314710-A-T
• NM_016586.3:c.455T>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_016586.3(MBIP):​c.455T>A​(p.Ile152Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: MBIP NM_016586.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.16
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.834

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.455T>A	p.Ile152Lys	missense	Exon 3 of 9	NP_057670.2	Q9NS73-1
	MBIP	NM_001144891.2		c.455T>A	p.Ile152Lys	missense	Exon 3 of 9	NP_001138363.1	Q9NS73-5
	MBIP	NM_001308110.2		c.455T>A	p.Ile152Lys	missense	Exon 3 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.455T>A	p.Ile152Lys	missense	Exon 3 of 9	ENSP00000399718.2	Q9NS73-1
	MBIP	ENST00000318473.11	TSL:1	c.455T>A	p.Ile152Lys	missense	Exon 3 of 9	ENSP00000324444.5	Q9NS73-5
	MBIP	ENST00000359527.11	TSL:1	c.455T>A	p.Ile152Lys	missense	Exon 3 of 8	ENSP00000352517.5	Q9NS73-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461262 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726922

African (AFR) AF: 0.00 AC: 0 AN: 33430

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111680

Other (OTH) AF: 0.0000166 AC: 1 AN: 60360

GnomAD4 genome Cov.: 32

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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	26
DANN	Benign	0.96
DEOGEN2	Uncertain	0.43	T
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.2
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-6.4	D
REVEL	Uncertain	0.57
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.59		Loss of sheet (P = 3e-04)
MVP		0.73
MPC		0.60
ClinPred		0.99	D
GERP RS		6.2
Varity_R		0.82
gMVP		0.83
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr14-36783916;