Genetic Variant MIIP:p.Gln149Glu (chr1-12022425-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_021933.4(MIIP):c.445C>G(p.Gln149Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,421,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MIIP
NM_021933.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.36

Variant links:

Genes affected

MIIP (HGNC:25715): (migration and invasion inhibitory protein) This gene encodes a protein that interacts with the oncogene protein insulin-like growth factor binding protein 2 and may function as an inhibitor of cell migration and invasion. This protein also interacts with the cell division protein 20 and may be involved in regulating mitotic progression. This protein may function as a tumor suppressor by inhibiting the growth or certain cancers. [provided by RefSeq, Sep 2011]

MIIP links:

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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=0.069399476).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIIP	NM_021933.4 link	c.445C>G	p.Gln149Glu	missense_variant	Exon 3 of 10	ENST00000235332.6	NP_068752.2	Q5JXC2-1
MIIP	XM_011541895.2 link	c.445C>G	p.Gln149Glu	missense_variant	Exon 3 of 10		XP_011540197.1	Q5JXC2-1
MIIP	XM_011541896.2 link	c.445C>G	p.Gln149Glu	missense_variant	Exon 3 of 10		XP_011540198.1	Q5JXC2-1
MIIP	XM_005263487.5 link	c.445C>G	p.Gln149Glu	missense_variant	Exon 3 of 10		XP_005263544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MIIP	ENST00000235332.6 link	c.445C>G	p.Gln149Glu	missense_variant	Exon 3 of 10	1	NM_021933.4	ENSP00000235332.4	Q5JXC2-1
MIIP	ENST00000466860.5 link	n.204C>G		non_coding_transcript_exon_variant	Exon 1 of 6	5
MIIP	ENST00000478749.5 link	n.418C>G		non_coding_transcript_exon_variant	Exon 2 of 6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000488

AC:

AN:

204876

Hom.:

AF XY:

0.00000889

AC XY:

AN XY:

112504

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000108

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1421938

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

704932

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000183

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000758

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 11, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.445C>G (p.Q149E) alteration is located in exon 3 (coding exon 2) of the MIIP gene. This alteration results from a C to G substitution at nucleotide position 445, causing the glutamine (Q) at amino acid position 149 to be replaced by a glutamic acid (E). 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

0.081

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

8.2

DANN

Benign

0.41

DEOGEN2

Benign

0.0090

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.54

M_CAP

Benign

0.0036

MetaRNN

Benign

0.069

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.68

REVEL

Benign

0.11

Sift

Benign

0.46

Sift4G

Benign

0.97

Polyphen

0.63

Vest4

0.078

MutPred

0.12

Gain of ubiquitination at K151 (P = 0.0192);

MVP

0.17

MPC

0.12

ClinPred

0.085

GERP RS

2.5

Varity_R

0.030

gMVP

0.19

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over