12-30630896-G-A
Variant names:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1
The NM_006390.4(IPO8):c.3078C>T(p.Ser1026Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000057 in 1,613,562 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000060 ( 1 hom. )
Consequence
IPO8
NM_006390.4 synonymous
NM_006390.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.74
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 Benign. Variant got -9 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 12-30630896-G-A is Benign according to our data. Variant chr12-30630896-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3770900.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.74 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0000595 (87/1461404) while in subpopulation SAS AF= 0.000232 (20/86232). AF 95% confidence interval is 0.000153. There are 1 homozygotes in gnomad4_exome. There are 52 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IPO8 | NM_006390.4 | c.3078C>T | p.Ser1026Ser | synonymous_variant | Exon 25 of 25 | ENST00000256079.9 | NP_006381.2 | |
IPO8 | NM_001190995.2 | c.2463C>T | p.Ser821Ser | synonymous_variant | Exon 21 of 21 | NP_001177924.1 | ||
IPO8 | XM_017018691.3 | c.3027C>T | p.Ser1009Ser | synonymous_variant | Exon 25 of 25 | XP_016874180.1 | ||
IPO8 | XM_017018692.2 | c.2892C>T | p.Ser964Ser | synonymous_variant | Exon 24 of 24 | XP_016874181.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IPO8 | ENST00000256079.9 | c.3078C>T | p.Ser1026Ser | synonymous_variant | Exon 25 of 25 | 1 | NM_006390.4 | ENSP00000256079.4 | ||
IPO8 | ENST00000544829.5 | c.2463C>T | p.Ser821Ser | synonymous_variant | Exon 21 of 21 | 2 | ENSP00000444520.1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152158Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000518 AC: 13AN: 251168Hom.: 1 AF XY: 0.0000737 AC XY: 10AN XY: 135742
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GnomAD4 exome AF: 0.0000595 AC: 87AN: 1461404Hom.: 1 Cov.: 30 AF XY: 0.0000715 AC XY: 52AN XY: 727034
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74328
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Jan 01, 2025
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
IPO8: BP4, BP7 -
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at