1-12022869-A-T

Variant names:

• chr1-12022869-A-T
• rs2295283
• NM_021933.4:c.499A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021933.4(MIIP):​c.499A>T​(p.Lys167*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MIIP NM_021933.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.41
• Publications: 53 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIIP	NM_021933.4	c.499A>T	p.Lys167*	stop_gained	Exon 4 of 10	ENST00000235332.6	NP_068752.2
MIIP	XM_011541895.2	c.499A>T	p.Lys167*	stop_gained	Exon 4 of 10		XP_011540197.1
MIIP	XM_011541896.2	c.499A>T	p.Lys167*	stop_gained	Exon 4 of 10		XP_011540198.1
MIIP	XM_005263487.5	c.499A>T	p.Lys167*	stop_gained	Exon 4 of 10		XP_005263544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIIP	ENST00000235332.6	c.499A>T	p.Lys167*	stop_gained	Exon 4 of 10	1	NM_021933.4	ENSP00000235332.4
MIIP	ENST00000466860.5	n.258A>T		non_coding_transcript_exon_variant	Exon 2 of 6	5
MIIP	ENST00000478749.5	n.472A>T		non_coding_transcript_exon_variant	Exon 3 of 6	2
MIIP	ENST00000498685.5	n.6A>T		non_coding_transcript_exon_variant	Exon 1 of 6	2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1456766 Hom.: 0 Cov.: 46 AF XY: 0.00 AC XY: 0 AN XY: 724226

African (AFR) AF: 0.00 AC: 0 AN: 33392

American (AMR) AF: 0.00 AC: 0 AN: 44134

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26016

East Asian (EAS) AF: 0.00 AC: 0 AN: 39540

South Asian (SAS) AF: 0.00 AC: 0 AN: 85218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53114

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109376

Other (OTH) AF: 0.00 AC: 0 AN: 60212

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 189674

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	37
DANN	Uncertain	0.99
Eigen	Benign	0.024
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.16	N
PhyloP100		2.4
Vest4		0.066
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=61/139	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2295283; hg19: chr1-12082926;