12-30636974-GACTTT-G

Variant names:

• chr12-30636974-GACTTT-G
• NM_006390.4:c.2695+3_2695+7delAAAGT

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_006390.4(IPO8):​c.2695+3_2695+7delAAAGT variant causes a splice region, intron change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IPO8 NM_006390.4 splice_region, intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.31

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 12-30636974-GACTTT-G is Pathogenic according to our data. Variant chr12-30636974-GACTTT-G is described in ClinVar as [Pathogenic]. Clinvar id is 1064723.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO8	NM_006390.4	c.2695+3_2695+7delAAAGT		splice_region_variant, intron_variant	Intron 22 of 24	ENST00000256079.9	NP_006381.2
IPO8	NM_001190995.2	c.2080+3_2080+7delAAAGT		splice_region_variant, intron_variant	Intron 18 of 20		NP_001177924.1
IPO8	XM_017018691.3	c.2644+3_2644+7delAAAGT		splice_region_variant, intron_variant	Intron 22 of 24		XP_016874180.1
IPO8	XM_017018692.2	c.2509+3_2509+7delAAAGT		splice_region_variant, intron_variant	Intron 21 of 23		XP_016874181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPO8	ENST00000256079.9	c.2695+3_2695+7delAAAGT		splice_region_variant, intron_variant	Intron 22 of 24	1	NM_006390.4	ENSP00000256079.4
IPO8	ENST00000544829.5	c.2080+3_2080+7delAAAGT		splice_region_variant, intron_variant	Intron 18 of 20	2		ENSP00000444520.1
IPO8	ENST00000535598.1	c.166+3_166+7delAAAGT		splice_region_variant, intron_variant	Intron 1 of 2	3		ENSP00000446232.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

IPO8 related Connective tissue disorder Pathogenic:1

Apr 22, 2021

Biochemistry and Genetics Laboratory, University Hospital of Angers

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr12-30789908;