rs374821486

Variant names:

• chr1-12022209-C-T
• rs374821486
• NM_021933.4:c.229C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-12022209-C-T
• chr1-12022209-C-G

Variant summary

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

The NM_021933.4(MIIP):​c.229C>T​(p.Pro77Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,613,076 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: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000037 (0 hom.)
• Consequence: MIIP NM_021933.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0230
• Publications: 2 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=0.028141946).

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.229C>T	p.Pro77Ser	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.229C>T	p.Pro77Ser	missense	Exon 3 of 10	ENSP00000235332.4	Q5JXC2-1
	MIIP	ENST00000857909.1		c.229C>T	p.Pro77Ser	missense	Exon 3 of 10	ENSP00000527968.1
	MIIP	ENST00000857910.1		c.229C>T	p.Pro77Ser	missense	Exon 3 of 10	ENSP00000527969.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

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: 0.00143

GnomAD2 exomes AF: 0.0000763 AC: 19 AN: 248984 AF XY: 0.0000445

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000407

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000356

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000370 AC: 54 AN: 1460868 Hom.: 0 Cov.: 30 AF XY: 0.0000385 AC XY: 28 AN XY: 726724

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.000516 AC: 23 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26018

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53230

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

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1111558

Other (OTH) AF: 0.000182 AC: 11 AN: 60360

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152208 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74354

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.000327 AC: 5 AN: 15284

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00143 AC: 3 AN: 2092

Alfa AF: 0.000130 Hom.: 0

Bravo AF: 0.0000982

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.075
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.9
DANN	Benign	0.89
DEOGEN2	Benign	0.0018	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.76	N
PhyloP100		-0.023
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.054
Sift	Benign	0.50	T
Sift4G	Benign	0.84	T
Polyphen		0.047	B
Vest4		0.13
MVP		0.055
MPC		0.44
ClinPred		0.051	T
GERP RS		2.5
Varity_R		0.036
gMVP		0.096
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

dbSNP: rs374821486; hg19: chr1-12082266;