rs61762966

Variant names:

• chr6-43572565-C-T
• rs61762966
• NM_020750.3:c.241G>A
• XPO5 p.Gly81Ser

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_020750.3(XPO5):​c.241G>A​(p.Gly81Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0023 in 1,613,814 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (27 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (24 hom.)
• Consequence: XPO5 NM_020750.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.69
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026955009).
• BP6: Variant 6-43572565-C-T is Benign according to our data. Variant chr6-43572565-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 787830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0107 (1627/152150) while in subpopulation AFR AF = 0.0363 (1507/41496). AF 95% confidence interval is 0.0348. There are 27 homozygotes in GnomAd4. There are 757 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1627 AD gene.

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.241G>A	p.Gly81Ser	missense	Exon 3 of 32	NP_065801.1	Q9HAV4
	XPO5	NR_144392.2		n.415G>A		non_coding_transcript_exon	Exon 3 of 33

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPO5	ENST00000265351.12	TSL:1 MANE Select	c.241G>A	p.Gly81Ser	missense	Exon 3 of 32	ENSP00000265351.7	Q9HAV4
	XPO5	ENST00000943409.1		c.241G>A	p.Gly81Ser	missense	Exon 3 of 32	ENSP00000613468.1
	XPO5	ENST00000943413.1		c.241G>A	p.Gly81Ser	missense	Exon 3 of 32	ENSP00000613472.1

Frequencies

GnomAD3 genomes AF: 0.0107 AC: 1628 AN: 152032 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00472

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000417

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00314 AC: 783 AN: 249244 AF XY: 0.00271

Gnomad AFR exome AF: 0.0364

Gnomad AMR exome AF: 0.00403

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000434

Gnomad OTH exome AF: 0.00429

GnomAD4 exome AF: 0.00142 AC: 2077 AN: 1461664 Hom.: 24 Cov.: 30 AF XY: 0.00130 AC XY: 945 AN XY: 727120

African (AFR) AF: 0.0367 AC: 1229 AN: 33472

American (AMR) AF: 0.00461 AC: 206 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000220 AC: 19 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53388

Middle Eastern (MID) AF: 0.00485 AC: 28 AN: 5768

European-Non Finnish (NFE) AF: 0.000362 AC: 402 AN: 1111862

Other (OTH) AF: 0.00318 AC: 192 AN: 60366

GnomAD4 genome AF: 0.0107 AC: 1627 AN: 152150 Hom.: 27 Cov.: 32 AF XY: 0.0102 AC XY: 757 AN XY: 74392

African (AFR) AF: 0.0363 AC: 1507 AN: 41496

American (AMR) AF: 0.00471 AC: 72 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000417 AC: 2 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68014

Other (OTH) AF: 0.00994 AC: 21 AN: 2112

Alfa AF: 0.00456 Hom.: 16

Bravo AF: 0.0121

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000830

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Benign	0.85
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.79	T
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.4	N
PhyloP100		1.7
PrimateAI	Benign	0.34	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.051
Sift	Benign	0.59	T
Sift4G	Benign	0.82	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.065
gMVP		0.074
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs61762966;

hg19: chr6-43540302;