rs699937

Variant names:

• chr6-43573189-G-A
• rs699937
• NM_020750.3:c.227+291C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020750.3(XPO5):​c.227+291C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,136 control chromosomes in the GnomAD database, including 5,669 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (5669 hom., cov: 32)
• Consequence: XPO5 NM_020750.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.249
• Publications: 15 publications found

Genes affected

XPO5 (HGNC:17675): (exportin 5) This gene encodes a member of the karyopherin family that is required for the transport of small RNAs and double-stranded RNA-binding proteins from the nucleus to the cytoplasm. The encoded protein translocates cargo through the nuclear pore complex in a RanGTP-dependent process. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-43573189-G-A is Benign according to our data. Variant chr6-43573189-G-A is described in ClinVar as Benign. ClinVar VariationId is 1225218.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020750.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPO5	NM_020750.3	MANE Select	c.227+291C>T		intron	N/A	NP_065801.1	Q9HAV4
	XPO5	NR_144392.2		n.401+291C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPO5	ENST00000265351.12	TSL:1 MANE Select	c.227+291C>T		intron	N/A	ENSP00000265351.7	Q9HAV4
	XPO5	ENST00000943409.1		c.227+291C>T		intron	N/A	ENSP00000613468.1
	XPO5	ENST00000943413.1		c.227+291C>T		intron	N/A	ENSP00000613472.1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37956 AN: 152020 Hom.: 5665 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.0270

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.250 AC: 37964 AN: 152136 Hom.: 5669 Cov.: 32 AF XY: 0.253 AC XY: 18831 AN XY: 74378

African (AFR) AF: 0.108 AC: 4474 AN: 41522

American (AMR) AF: 0.301 AC: 4603 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 812 AN: 3468

East Asian (EAS) AF: 0.0270 AC: 140 AN: 5182

South Asian (SAS) AF: 0.270 AC: 1302 AN: 4820

European-Finnish (FIN) AF: 0.353 AC: 3735 AN: 10570

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21855 AN: 67982

Other (OTH) AF: 0.242 AC: 512 AN: 2112

Alfa AF: 0.295 Hom.: 9201

Bravo AF: 0.240

Asia WGS AF: 0.129 AC: 447 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.50
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs699937; hg19: chr6-43540926;