12-30636973-AGACTT-A

Position:

• chr12-30636973-AGACTT-A

Variant summary

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

The NM_006390.4(IPO8):​c.2695+4_2695+8del variant causes a splice donor 5th base, 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_donor_5th_base, 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 12-30636973-AGACTT-A is Pathogenic according to our data. Variant chr12-30636973-AGACTT-A is described in ClinVar as [Pathogenic]. Clinvar id is 1192309.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IPO8	NM_006390.4	c.2695+4_2695+8del		splice_donor_5th_base_variant, intron_variant		ENST00000256079.9	NP_006381.2
IPO8	NM_001190995.2	c.2080+4_2080+8del		splice_donor_5th_base_variant, intron_variant			NP_001177924.1
IPO8	XM_017018691.3	c.2644+4_2644+8del		splice_donor_5th_base_variant, intron_variant			XP_016874180.1
IPO8	XM_017018692.2	c.2509+4_2509+8del		splice_donor_5th_base_variant, intron_variant			XP_016874181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IPO8	ENST00000256079.9	c.2695+4_2695+8del		splice_donor_5th_base_variant, intron_variant		1	NM_006390.4	ENSP00000256079	P1
IPO8	ENST00000535598.1	c.168+4_168+8del		splice_donor_5th_base_variant, intron_variant		3		ENSP00000446232
IPO8	ENST00000544829.5	c.2080+4_2080+8del		splice_donor_5th_base_variant, intron_variant		2		ENSP00000444520

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

VISS syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 12, 2021

- -

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: chr12-30789907;