NM_021933.4:c.41A>G

Variant names:

• chr1-12021767-A-G
• rs143131861
• NM_021933.4:c.41A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021933.4(MIIP):​c.41A>G​(p.Asn14Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000049 in 1,613,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N14I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000048 (0 hom.)
• Consequence: MIIP NM_021933.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0770
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.031066805).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021933.4. 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
	MIIP	NM_021933.4	MANE Select	c.41A>G	p.Asn14Ser	missense	Exon 2 of 10	NP_068752.2	Q5JXC2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIIP	ENST00000235332.6	TSL:1 MANE Select	c.41A>G	p.Asn14Ser	missense	Exon 2 of 10	ENSP00000235332.4	Q5JXC2-1
	MIIP	ENST00000857909.1		c.41A>G	p.Asn14Ser	missense	Exon 2 of 10	ENSP00000527968.1
	MIIP	ENST00000857910.1		c.41A>G	p.Asn14Ser	missense	Exon 2 of 10	ENSP00000527969.1

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000482 AC: 12 AN: 248954 AF XY: 0.0000445

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000200

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000479 AC: 70 AN: 1460876 Hom.: 0 Cov.: 31 AF XY: 0.0000509 AC XY: 37 AN XY: 726736

African (AFR) AF: 0.0000897 AC: 3 AN: 33462

American (AMR) AF: 0.0000224 AC: 1 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.000804 AC: 21 AN: 26114

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53014

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5356

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1111964

Other (OTH) AF: 0.000116 AC: 7 AN: 60342

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152200 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74350

African (AFR) AF: 0.0000724 AC: 3 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000113 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000577 AC: 7

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.091
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	12
DANN	Benign	0.92
DEOGEN2	Benign	0.0084	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.76	N
PhyloP100		-0.077
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.054
Sift	Benign	0.33	T
Sift4G	Benign	0.38	T
Polyphen		0.026	B
Vest4		0.23
MutPred		0.28		Gain of disorder (P = 0.0309)
MVP		0.088
MPC		0.073
ClinPred		0.019	T
GERP RS		-0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.045
gMVP		0.21
Mutation Taster		=92/8	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: rs143131861; hg19: chr1-12081824;