dbSNP rs34324334: XPO5:p.Ser241Asn (chr6-43567281-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020750.3(XPO5):c.722G>A(p.Ser241Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.071 in 1,613,612 control chromosomes in the GnomAD database, including 4,424 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 344 hom., cov: 32)

Exomes 𝑓: 0.073 ( 4080 hom. )

Consequence

XPO5
NM_020750.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.221

Publications

29 publications found

Variant links:

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]

XPO5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002454251).

BP6

Variant 6-43567281-C-T is Benign according to our data. Variant chr6-43567281-C-T is described in ClinVar as Benign. ClinVar VariationId is 1282374.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPO5	NM_020750.3 link	c.722G>A	p.Ser241Asn	missense_variant	Exon 7 of 32	ENST00000265351.12	NP_065801.1
XPO5	NR_144392.2 link	n.896G>A		non_coding_transcript_exon_variant	Exon 7 of 33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPO5	ENST00000265351.12 link	c.722G>A	p.Ser241Asn	missense_variant	Exon 7 of 32	1	NM_020750.3	ENSP00000265351.7

Frequencies

GnomAD3 genomes

AF:

0.0560

AC:

8517

AN:

152088

Hom.:

344

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0141

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.0574

Gnomad ASJ

AF:

0.0556

Gnomad EAS

AF:

0.000960

Gnomad SAS

AF:

0.0543

Gnomad FIN

AF:

0.111

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0765

Gnomad OTH

AF:

0.0535

GnomAD2 exomes

AF:

0.0626

AC:

15582

AN:

248974

AF XY:

0.0637

show subpopulations

Gnomad AFR exome

AF:

0.0140

Gnomad AMR exome

AF:

0.0582

Gnomad ASJ exome

AF:

0.0562

Gnomad EAS exome

AF:

0.000389

Gnomad FIN exome

AF:

0.102

Gnomad NFE exome

AF:

0.0744

Gnomad OTH exome

AF:

0.0720

GnomAD4 exome

AF:

0.0726

AC:

106097

AN:

1461406

Hom.:

4080

Cov.:

AF XY:

0.0722

AC XY:

52513

AN XY:

726980

show subpopulations

African (AFR)

AF:

0.00992

AC:

332

AN:

33478

American (AMR)

AF:

0.0594

AC:

2652

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.0586

AC:

1532

AN:

26124

East Asian (EAS)

AF:

0.000126

AC:

AN:

39698

South Asian (SAS)

AF:

0.0576

AC:

4965

AN:

86204

European-Finnish (FIN)

AF:

0.0953

AC:

5087

AN:

53388

Middle Eastern (MID)

AF:

0.0461

AC:

266

AN:

5766

European-Non Finnish (NFE)

AF:

0.0786

AC:

87399

AN:

1111700

Other (OTH)

AF:

0.0639

AC:

3859

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

5151

10302

15454

20605

25756

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3248

6496

9744

12992

16240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0560

AC:

8517

AN:

152206

Hom.:

344

Cov.:

AF XY:

0.0572

AC XY:

4259

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0140

AC:

583

AN:

41526

American (AMR)

AF:

0.0573

AC:

875

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.0556

AC:

193

AN:

3472

East Asian (EAS)

AF:

0.000963

AC:

AN:

5194

South Asian (SAS)

AF:

0.0545

AC:

263

AN:

4824

European-Finnish (FIN)

AF:

0.111

AC:

1170

AN:

10582

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0765

AC:

5203

AN:

68018

Other (OTH)

AF:

0.0530

AC:

112

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

422

844

1267

1689

2111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0678

Hom.:

1271

Bravo

AF:

0.0506

TwinsUK

AF:

0.0796

AC:

295

ALSPAC

AF:

0.0758

AC:

292

ESP6500AA

AF:

0.0132

AC:

ESP6500EA

AF:

0.0719

AC:

594

ExAC

AF:

0.0613

AC:

7407

Asia WGS

AF:

0.0250

AC:

AN:

3478

EpiCase

AF:

0.0719

EpiControl

AF:

0.0733

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.042

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.71

MetaRNN

Benign

0.0025

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.46

PhyloP100

-0.22

PrimateAI

Benign

0.43

PROVEAN

Benign

0.17

REVEL

Benign

0.11

Sift

Benign

0.82

Sift4G

Benign

0.28

Polyphen

0.0020

Vest4

0.080

MPC

0.35

ClinPred

0.0011

GERP RS

-1.9

Varity_R

0.050

gMVP

0.13

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over