Genetic Variant XPO7:c.426+12A>T (chr8-21970322-A-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP4_StrongBS2

The NM_015024.5(XPO7):c.426+12A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,457,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

XPO7
NM_015024.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.14

Variant links:

Genes affected

XPO7 (HGNC:14108): (exportin 7) The transport of protein and large RNAs through the nuclear pore complexes (NPC) is an energy-dependent and regulated process. The import of proteins with a nuclear localization signal (NLS) is accomplished by recognition of one or more clusters of basic amino acids by the importin-alpha/beta complex; see MIM 600685 and MIM 602738. The small GTPase RAN (MIM 601179) plays a key role in NLS-dependent protein import. RAN-binding protein-16 is a member of the importin-beta superfamily of nuclear transport receptors.[supplied by OMIM, Jul 2002]

XPO7 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
XPO7	NM_015024.5 link	c.426+12A>T	intron_variant	Intron 4 of 27	ENST00000252512.14	NP_055839.3	Q9UIA9
XPO7	NM_001100161.2 link	c.426+12A>T	intron_variant	Intron 4 of 27		NP_001093631.1
XPO7	NM_001362802.2 link	c.426+12A>T	intron_variant	Intron 4 of 26		NP_001349731.1
XPO7	NR_156173.2 link	n.535+12A>T	intron_variant	Intron 4 of 28

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
XPO7	ENST00000252512.14 link	c.426+12A>T	intron_variant	Intron 4 of 27	1	NM_015024.5	ENSP00000252512.9	Q9UIA9
XPO7	ENST00000518017.1 link	n.621+12A>T	intron_variant	Intron 4 of 6	1
XPO7	ENST00000433566.8 link	c.429+12A>T	intron_variant	Intron 4 of 27	5		ENSP00000410249.3	E7ESC6
XPO7	ENST00000521303.5 link	c.438+12A>T	intron_variant	Intron 4 of 5	5		ENSP00000429290.1	H0YBE1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1457996

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

725036

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:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.048

DANN

Benign

0.57

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over