1-12022186-G-A

Position:

• chr1-12022186-G-A

Variant summary

Our verdict is Likely benign. Variant got -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. 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: 0.0000062 (0 hom.)
• Consequence: MIIP NM_021933.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.354

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

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=0.03434357).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIIP	NM_021933.4	c.206G>A	p.Gly69Asp	missense_variant	3/10	ENST00000235332.6	NP_068752.2
MIIP	XM_011541895.2	c.206G>A	p.Gly69Asp	missense_variant	3/10		XP_011540197.1
MIIP	XM_011541896.2	c.206G>A	p.Gly69Asp	missense_variant	3/10		XP_011540198.1
MIIP	XM_005263487.5	c.206G>A	p.Gly69Asp	missense_variant	3/10		XP_005263544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIIP	ENST00000235332.6	c.206G>A	p.Gly69Asp	missense_variant	3/10	1	NM_021933.4	ENSP00000235332	P1
MIIP	ENST00000478749.5	n.179G>A		non_coding_transcript_exon_variant	2/6	2
MIIP	ENST00000466860.5			upstream_gene_variant		5

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

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: 0.00000809

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 15, 2023

The c.206G>A (p.G69D) alteration is located in exon 3 (coding exon 2) of the MIIP gene. This alteration results from a G to A substitution at nucleotide position 206, causing the glycine (G) at amino acid position 69 to be replaced by an aspartic acid (D). 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	0.077
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
MutationTaster	Benign	1.0	N;N
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

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.

Other links and lift over

hg19: chr1-12082243;