1-12022186-G-A

Variant names:

• chr1-12022186-G-A
• NM_021933.4:c.206G>A

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.206G>A​(p.Gly69Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,446 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: MIIP NM_021933.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.354
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03434357).

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.206G>A	p.Gly69Asp	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.206G>A	p.Gly69Asp	missense	Exon 3 of 10	ENSP00000235332.4	Q5JXC2-1
	MIIP	ENST00000857909.1		c.206G>A	p.Gly69Asp	missense	Exon 3 of 10	ENSP00000527968.1
	MIIP	ENST00000857910.1		c.206G>A	p.Gly69Asp	missense	Exon 3 of 10	ENSP00000527969.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461446 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727040

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111846

Other (OTH) AF: 0.00 AC: 0 AN: 60386

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	Benign	0.077
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.52
DANN	Benign	0.71
DEOGEN2	Benign	0.00034	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.10	N
PhyloP100		0.35
PrimateAI	Benign	0.28	T
PROVEAN	Benign	1.5	N
REVEL	Benign	0.056
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.053
MutPred		0.13		Loss of methylation at R68 (P = 0.044)
MVP		0.030
MPC		0.12
ClinPred		0.026	T
GERP RS		0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.020
gMVP		0.058
Mutation Taster		=98/2	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

hg19: chr1-12082243;