NM_021933.4:c.235G>T

Variant names:

• chr1-12022215-G-T
• rs760757327
• NM_021933.4:c.235G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_021933.4(MIIP):​c.235G>T​(p.Ala79Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,613,000 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. A79T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: MIIP NM_021933.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.340
• Publications: 0 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015622675).

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.235G>T	p.Ala79Ser	missense	Exon 3 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.235G>T	p.Ala79Ser	missense	Exon 3 of 10	ENSP00000235332.4	Q5JXC2-1
	MIIP	ENST00000857909.1		c.235G>T	p.Ala79Ser	missense	Exon 3 of 10	ENSP00000527968.1
	MIIP	ENST00000857910.1		c.235G>T	p.Ala79Ser	missense	Exon 3 of 10	ENSP00000527969.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000683 AC: 17 AN: 248778 AF XY: 0.0000742

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000383 AC: 56 AN: 1460808 Hom.: 0 Cov.: 30 AF XY: 0.0000509 AC XY: 37 AN XY: 726702

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44580

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26012

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000592 AC: 51 AN: 86172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53236

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111532

Other (OTH) AF: 0.0000331 AC: 2 AN: 60358

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152192 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74336

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000179 Hom.: 1

Bravo AF: 0.00000378

ExAC AF: 0.0000824 AC: 10

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	0.084
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.12
DANN	Benign	0.74
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.76	N
PhyloP100		-0.34
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.021
Sift	Benign	0.77	T
Sift4G	Benign	0.71	T
Polyphen		0.24	B
Vest4		0.060
MutPred		0.11		Gain of phosphorylation at A79 (P = 0.0263)
MVP		0.072
MPC		0.11
ClinPred		0.034	T
GERP RS		-0.46
Varity_R		0.022
gMVP		0.12
Mutation Taster		=100/0	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: rs760757327; hg19: chr1-12082272;