1-12022099-G-T

Variant names:

• chr1-12022099-G-T
• rs775769116
• NM_021933.4:c.119G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021933.4(MIIP):​c.119G>T​(p.Ser40Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S40N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MIIP NM_021933.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13055319).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIIP	NM_021933.4	c.119G>T	p.Ser40Ile	missense_variant	Exon 3 of 10	ENST00000235332.6	NP_068752.2
MIIP	XM_011541895.2	c.119G>T	p.Ser40Ile	missense_variant	Exon 3 of 10		XP_011540197.1
MIIP	XM_011541896.2	c.119G>T	p.Ser40Ile	missense_variant	Exon 3 of 10		XP_011540198.1
MIIP	XM_005263487.5	c.119G>T	p.Ser40Ile	missense_variant	Exon 3 of 10		XP_005263544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIIP	ENST00000235332.6	c.119G>T	p.Ser40Ile	missense_variant	Exon 3 of 10	1	NM_021933.4	ENSP00000235332.4
MIIP	ENST00000478749.5	n.92G>T		non_coding_transcript_exon_variant	Exon 2 of 6	2
MIIP	ENST00000466860.5	n.-123G>T		upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461192 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726908

Gnomad4 AFR exome AF: 0.0000597

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152166 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74332

Gnomad4 AFR AF: 0.0000966

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0087	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.021
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.020	D
Polyphen		0.93	P
Vest4		0.22
MVP		0.20
MPC		0.36
ClinPred		0.73	D
GERP RS		0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.11
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs775769116; hg19: chr1-12082156;