chr1-12022869-A-T

Position:

• chr1-12022869-A-T

Variant summary

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

The ENST00000235332.6(MIIP):​c.499A>T​(p.Lys167Ter) 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 ENST00000235332.6 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.41

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIIP	NM_021933.4	c.499A>T	p.Lys167Ter	stop_gained	4/10	ENST00000235332.6	NP_068752.2
MIIP	XM_011541895.2	c.499A>T	p.Lys167Ter	stop_gained	4/10		XP_011540197.1
MIIP	XM_011541896.2	c.499A>T	p.Lys167Ter	stop_gained	4/10		XP_011540198.1
MIIP	XM_005263487.5	c.499A>T	p.Lys167Ter	stop_gained	4/10		XP_005263544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIIP	ENST00000235332.6	c.499A>T	p.Lys167Ter	stop_gained	4/10	1	NM_021933.4	ENSP00000235332	P1
MIIP	ENST00000466860.5	n.258A>T		non_coding_transcript_exon_variant	2/6	5
MIIP	ENST00000478749.5	n.472A>T		non_coding_transcript_exon_variant	3/6	2
MIIP	ENST00000498685.5	n.6A>T		non_coding_transcript_exon_variant	1/6	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

Gnomad4 AFR exome AF: 0.00

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: 0.00

GnomAD4 genome Cov.: 30

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
MutationTaster	Benign	4.1e-11	P;P
Vest4		0.066
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs2295283; hg19: chr1-12082926;