1-201848472-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_018085.5(IPO9):​c.392C>T​(p.Ala131Val) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 32)

Consequence

IPO9
NM_018085.5 missense

Scores

8
8
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.82
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.83

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IPO9NM_018085.5 linkc.392C>T p.Ala131Val missense_variant Exon 4 of 24 ENST00000361565.9 NP_060555.2 Q96P70

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IPO9ENST00000361565.9 linkc.392C>T p.Ala131Val missense_variant Exon 4 of 24 1 NM_018085.5 ENSP00000354742.4 Q96P70
IPO9ENST00000464348.5 linkn.564C>T non_coding_transcript_exon_variant Exon 5 of 7 5
IPO9ENST00000479374.1 linkn.213C>T non_coding_transcript_exon_variant Exon 3 of 4 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
May 08, 2023
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Gene of Uncertain Significance -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.70
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Pathogenic
0.14
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.73
D
Eigen
Pathogenic
0.69
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.039
D
MetaRNN
Pathogenic
0.83
D
MetaSVM
Benign
-0.58
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Pathogenic
0.86
D
PROVEAN
Uncertain
-2.7
D
REVEL
Uncertain
0.37
Sift
Uncertain
0.0070
D
Sift4G
Uncertain
0.014
D
Polyphen
0.99
D
Vest4
0.80
MutPred
0.37
Gain of MoRF binding (P = 0.0981);
MVP
0.57
MPC
0.97
ClinPred
0.95
D
GERP RS
6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2
Varity_R
0.65
gMVP
0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-201817600; API