1-201829304-T-G

Variant names:

• chr1-201829304-T-G
• NM_018085.5:c.95T>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018085.5(IPO9):​c.95T>G​(p.Ile32Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: IPO9 NM_018085.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.39
• Publications: 0 publications found

Genes affected

IPO9 (HGNC:19425): (importin 9) Enables nuclear import signal receptor activity. Involved in protein import into nucleus. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

IPO9-AS1 (HGNC:40892): (IPO9 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.821

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018085.5. 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
	IPO9	NM_018085.5	MANE Select	c.95T>G	p.Ile32Ser	missense	Exon 1 of 24	NP_060555.2
	IPO9-AS1	NR_046696.1		n.256A>C		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IPO9	ENST00000361565.9	TSL:1 MANE Select	c.95T>G	p.Ile32Ser	missense	Exon 1 of 24	ENSP00000354742.4	Q96P70
	IPO9	ENST00000926157.1		c.95T>G	p.Ile32Ser	missense	Exon 1 of 25	ENSP00000596216.1
	IPO9	ENST00000926161.1		c.95T>G	p.Ile32Ser	missense	Exon 1 of 24	ENSP00000596220.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.69	D
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.93	D
M_CAP	Pathogenic	0.35	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.8	L
PhyloP100		6.4
PrimateAI	Pathogenic	0.96	D
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.026	D
Polyphen		0.98	D
Vest4		0.82
MutPred		0.47		Gain of disorder (P = 0.0032)
MVP		0.70
MPC		0.95
ClinPred		0.99	D
GERP RS		5.4
PromoterAI		-0.044	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.90
gMVP		0.63
Mutation Taster		=19/81	disease causing

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

Other links and lift over

hg19: chr1-201798432;