Variant 1-12022861-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021933.4(MIIP):c.491C>T(p.Ala164Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,838 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MIIP
NM_021933.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0130

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039254427).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MIIP	NM_021933.4 linkuse as main transcript	c.491C>T	p.Ala164Val	missense_variant	4/10	ENST00000235332.6	NP_068752.2
MIIP	XM_011541895.2 linkuse as main transcript	c.491C>T	p.Ala164Val	missense_variant	4/10		XP_011540197.1
MIIP	XM_011541896.2 linkuse as main transcript	c.491C>T	p.Ala164Val	missense_variant	4/10		XP_011540198.1
MIIP	XM_005263487.5 linkuse as main transcript	c.491C>T	p.Ala164Val	missense_variant	4/10		XP_005263544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIIP	ENST00000235332.6 linkuse as main transcript	c.491C>T	p.Ala164Val	missense_variant	4/10	1	NM_021933.4	ENSP00000235332	P1	Q5JXC2-1
MIIP	ENST00000466860.5 linkuse as main transcript	n.250C>T		non_coding_transcript_exon_variant	2/6	5
MIIP	ENST00000478749.5 linkuse as main transcript	n.464C>T		non_coding_transcript_exon_variant	3/6	2
MIIP	ENST00000498685.5 linkuse as main transcript			upstream_gene_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1456838

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724244

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:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 04, 2022

The c.491C>T (p.A164V) alteration is located in exon 4 (coding exon 3) of the MIIP gene. This alteration results from a C to T substitution at nucleotide position 491, causing the alanine (A) at amino acid position 164 to be replaced by a valine (V). 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

0.097

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

8.1

DANN

Benign

0.95

DEOGEN2

Benign

0.0020

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.56

M_CAP

Benign

0.0035

MetaRNN

Benign

0.039

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.2

REVEL

Benign

0.025

Sift

Benign

0.16

Sift4G

Benign

0.37

Polyphen

0.052

Vest4

0.034

MutPred

0.17

Gain of relative solvent accessibility (P = 0.0082);

MVP

0.11

MPC

0.10

ClinPred

0.033

GERP RS

0.068

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.020

gMVP

0.12

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over