NM_006390.4:c.2952C>G

Variant summary

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

The NM_006390.4(IPO8):ā€‹c.2952C>Gā€‹(p.Ser984Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,672 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

IPO8
NM_006390.4 missense

Scores

1
7
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.326
Variant links:
Genes affected
IPO8 (HGNC:9853): (importin 8) The importin-alpha/beta complex and the GTPase Ran mediate nuclear import of proteins with a classical nuclear localization signal. The protein encoded by this gene is a member of a class of approximately 20 potential Ran targets that share a sequence motif related to the Ran-binding site of importin-beta. This protein binds to the nuclear pore complex and, along with RanGTP and RANBP1, inhibits the GAP stimulation of the Ran GTPase. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

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ACMG classification

Classification made for transcript

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 rank MANE Protein UniProt
IPO8NM_006390.4 linkc.2952C>G p.Ser984Arg missense_variant Exon 24 of 25 ENST00000256079.9 NP_006381.2 O15397-1
IPO8NM_001190995.2 linkc.2337C>G p.Ser779Arg missense_variant Exon 20 of 21 NP_001177924.1 O15397-2
IPO8XM_017018691.3 linkc.2901C>G p.Ser967Arg missense_variant Exon 24 of 25 XP_016874180.1
IPO8XM_017018692.2 linkc.2766C>G p.Ser922Arg missense_variant Exon 23 of 24 XP_016874181.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IPO8ENST00000256079.9 linkc.2952C>G p.Ser984Arg missense_variant Exon 24 of 25 1 NM_006390.4 ENSP00000256079.4 O15397-1
IPO8ENST00000544829.5 linkc.2337C>G p.Ser779Arg missense_variant Exon 20 of 21 2 ENSP00000444520.1 O15397-2
IPO8ENST00000535598.1 linkc.423C>G p.Ser141Arg missense_variant Exon 3 of 3 3 ENSP00000446232.1 H0YH64

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000799
AC:
2
AN:
250378
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135324
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1460672
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
726668
show subpopulations
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000165
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.67
BayesDel_addAF
Benign
-0.014
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
14
DANN
Uncertain
0.99
DEOGEN2
Benign
0.17
T;.
Eigen
Benign
-0.88
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.34
N
LIST_S2
Benign
0.82
T;T
M_CAP
Benign
0.063
D
MetaRNN
Uncertain
0.57
D;D
MetaSVM
Benign
-0.48
T
MutationAssessor
Uncertain
2.4
M;.
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-2.2
N;N
REVEL
Uncertain
0.38
Sift
Uncertain
0.012
D;D
Sift4G
Uncertain
0.044
D;T
Polyphen
0.77
P;.
Vest4
0.62
MutPred
0.50
Gain of solvent accessibility (P = 0.1185);.;
MVP
0.54
MPC
0.37
ClinPred
0.75
D
GERP RS
-7.9
Varity_R
0.23
gMVP
0.56

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs746079753; hg19: chr12-30784893; API