1-12022306-C-T

Position:

• chr1-12022306-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_021933.4(MIIP):​c.326C>T​(p.Pro109Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000049 in 1,613,790 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000035 (0 hom.)
• Consequence: MIIP NM_021933.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.35

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.014510989).
• BP6: Variant 1-12022306-C-T is Benign according to our data. Variant chr1-12022306-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2472777.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIIP	NM_021933.4	c.326C>T	p.Pro109Leu	missense_variant	3/10	ENST00000235332.6	NP_068752.2
MIIP	XM_011541895.2	c.326C>T	p.Pro109Leu	missense_variant	3/10		XP_011540197.1
MIIP	XM_011541896.2	c.326C>T	p.Pro109Leu	missense_variant	3/10		XP_011540198.1
MIIP	XM_005263487.5	c.326C>T	p.Pro109Leu	missense_variant	3/10		XP_005263544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIIP	ENST00000235332.6	c.326C>T	p.Pro109Leu	missense_variant	3/10	1	NM_021933.4	ENSP00000235332	P1
MIIP	ENST00000466860.5	n.85C>T		non_coding_transcript_exon_variant	1/6	5
MIIP	ENST00000478749.5	n.299C>T		non_coding_transcript_exon_variant	2/6	2

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 152042 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000532

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000642 AC: 16 AN: 249286 Hom.: 0 AF XY: 0.0000740 AC XY: 10 AN XY: 135178

Gnomad AFR exome AF: 0.000438

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000268

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000349 AC: 51 AN: 1461630 Hom.: 0 Cov.: 33 AF XY: 0.0000371 AC XY: 27 AN XY: 727122

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.000184 AC: 28 AN: 152160 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74400

Gnomad4 AFR AF: 0.000530

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000299 Hom.: 0

Bravo AF: 0.000193

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000659 AC: 8

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 14, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.0060
DANN	Benign	0.78
DEOGEN2	Benign	0.0038	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0052	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.14	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.055
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0080	B
Vest4		0.031
MVP		0.030
MPC		0.096
ClinPred		0.019	T
GERP RS		-7.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.021
gMVP		0.12

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

LitVar

Other links and lift over

dbSNP: rs150131592; hg19: chr1-12082363; COSMIC: COSV99337713; COSMIC: COSV99337713;