1-12022861-C-T

Variant names:

• chr1-12022861-C-T
• NM_021933.4:c.491C>T

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.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. 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: 6.9e-7 (0 hom.)
• Consequence: MIIP NM_021933.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0130
• 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=0.039254427).

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.491C>T	p.Ala164Val	missense	Exon 4 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.491C>T	p.Ala164Val	missense	Exon 4 of 10	ENSP00000235332.4	Q5JXC2-1
	MIIP	ENST00000857909.1		c.491C>T	p.Ala164Val	missense	Exon 4 of 10	ENSP00000527968.1
	MIIP	ENST00000857910.1		c.491C>T	p.Ala164Val	missense	Exon 4 of 10	ENSP00000527969.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1456838 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724244

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33354

American (AMR) AF: 0.00 AC: 0 AN: 44264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26008

East Asian (EAS) AF: 0.00 AC: 0 AN: 39538

South Asian (SAS) AF: 0.00 AC: 0 AN: 85050

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53112

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109506

Other (OTH) AF: 0.00 AC: 0 AN: 60246

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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	0.097
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.1
DANN	Benign	0.95
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.013
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.025
Sift	Benign	0.16	T
Sift4G	Benign	0.37	T
Polyphen		0.052	B
Vest4		0.034
MutPred		0.17		Gain of relative solvent accessibility (P = 0.0082)
MVP		0.11
MPC		0.10
ClinPred		0.033	T
GERP RS		0.068
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.020
gMVP		0.12
Mutation Taster		=97/3	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: chr1-12082918;