Variant 12-30634159-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_ModerateBP6BS1

The NM_006390.4(IPO8):c.2823G>A(p.Ala941Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000477 in 1,613,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

IPO8
NM_006390.4 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0420

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]

IPO8 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 12-30634159-C-T is Benign according to our data. Variant chr12-30634159-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3054391.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000506 (74/1461720) while in subpopulation AMR AF= 0.0000671 (3/44718). AF 95% confidence interval is 0.0000452. There are 0 homozygotes in gnomad4_exome. There are 37 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO8	NM_006390.4 link	c.2823G>A	p.Ala941Ala	synonymous_variant	Exon 23 of 25	ENST00000256079.9	NP_006381.2	O15397-1
IPO8	NM_001190995.2 link	c.2208G>A	p.Ala736Ala	synonymous_variant	Exon 19 of 21		NP_001177924.1	O15397-2
IPO8	XM_017018691.3 link	c.2772G>A	p.Ala924Ala	synonymous_variant	Exon 23 of 25		XP_016874180.1
IPO8	XM_017018692.2 link	c.2637G>A	p.Ala879Ala	synonymous_variant	Exon 22 of 24		XP_016874181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IPO8	ENST00000256079.9 link	c.2823G>A	p.Ala941Ala	synonymous_variant	Exon 23 of 25	1	NM_006390.4	ENSP00000256079.4	O15397-1
IPO8	ENST00000544829.5 link	c.2208G>A	p.Ala736Ala	synonymous_variant	Exon 19 of 21	2		ENSP00000444520.1	O15397-2
IPO8	ENST00000535598.1 link	c.294G>A	p.Ala98Ala	synonymous_variant	Exon 2 of 3	3		ENSP00000446232.1	H0YH64

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000796

AC:

AN:

251316

Hom.:

AF XY:

0.000110

AC XY:

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000506

AC:

AN:

1461720

Hom.:

Cov.:

AF XY:

0.0000509

AC XY:

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000567

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000965

Hom.:

Bravo

AF:

0.0000264

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

IPO8-related disorder

Benign:1

Jun 29, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.53

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over