chr8-22002914-T-G

Variant names:

• chr8-22002914-T-G
• rs3816786
• NM_015024.5:c.2944-305T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001100161.2(XPO7):​c.2971-305T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: XPO7 NM_001100161.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.433
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• prostate cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000295189 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100161.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPO7	NM_015024.5	MANE Select	c.2944-305T>G		intron	N/A	NP_055839.3
	XPO7	NM_001100161.2		c.2971-305T>G		intron	N/A	NP_001093631.1
	XPO7	NM_001362802.2		c.2878-305T>G		intron	N/A	NP_001349731.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPO7	ENST00000252512.14	TSL:1 MANE Select	c.2944-305T>G		intron	N/A	ENSP00000252512.9
	XPO7	ENST00000433566.8	TSL:5	c.2947-305T>G		intron	N/A	ENSP00000410249.3
	XPO7	ENST00000879832.1		c.2923-305T>G		intron	N/A	ENSP00000549891.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 64980 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 34062

African (AFR) AF: 0.00 AC: 0 AN: 1436

American (AMR) AF: 0.00 AC: 0 AN: 2816

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2032

East Asian (EAS) AF: 0.00 AC: 0 AN: 2856

South Asian (SAS) AF: 0.00 AC: 0 AN: 7642

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 324

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 40354

Other (OTH) AF: 0.00 AC: 0 AN: 3994

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	17
DANN	Benign	0.58
PhyloP100		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.34		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.34		Position offset: -5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3816786; hg19: chr8-21860425;