Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The ENST00000263032.5(NXF5):n.697C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000423 in 1,206,403 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 160 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., 12 hem., cov: 20)

Exomes 𝑓: 0.00043 ( 0 hom. 148 hem. )

Consequence

NXF5
ENST00000263032.5 non_coding_transcript_exon

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 1.91

Publications

5 publications found

Variant links:

Genes affected

NXF5 (HGNC:):

NXF5 links:

NXF5 (HGNC:8075): (nuclear RNA export factor 5) This gene is one member of a family of nuclear RNA export factor genes. Most transcript variants are candidates for nonsense-mediated decay (NMD) and may not express proteins in vivo. [provided by RefSeq, Sep 2022]

NXF5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.28517944).

BS2

High Hemizygotes in GnomAd4 at 12 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000263032.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank
NXF5	NR_028089.1	n.697C>T	non_coding_transcript_exon	Exon 7 of 19
NXF5	NR_159736.1	n.508C>T	non_coding_transcript_exon	Exon 5 of 17
NXF5	NR_159737.1	n.508C>T	non_coding_transcript_exon	Exon 5 of 17

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
NXF5	ENST00000263032.5	TSL:1	n.697C>T	non_coding_transcript_exon	Exon 7 of 19
NXF5	ENST00000332614.6	TSL:1	n.508C>T	non_coding_transcript_exon	Exon 5 of 17
NXF5	ENST00000361330.5	TSL:1	n.508C>T	non_coding_transcript_exon	Exon 5 of 17

Frequencies

GnomAD3 genomes

AF:

0.000397

AC:

AN:

108436

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000270

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000291

Gnomad SAS

AF:

0.00127

Gnomad FIN

AF:

0.00106

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000478

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000402

AC:

AN:

178929

AF XY:

0.000403

show subpopulations

Gnomad AFR exome

AF:

0.0000802

Gnomad AMR exome

AF:

0.0000739

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000725

Gnomad FIN exome

AF:

0.00102

Gnomad NFE exome

AF:

0.000526

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000425

AC:

467

AN:

1097915

Hom.:

Cov.:

AF XY:

0.000407

AC XY:

148

AN XY:

363325

show subpopulations

African (AFR)

AF:

0.000379

AC:

AN:

26395

American (AMR)

AF:

0.0000284

AC:

AN:

35187

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19365

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.000370

AC:

AN:

54087

European-Finnish (FIN)

AF:

0.00143

AC:

AN:

40528

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4129

European-Non Finnish (NFE)

AF:

0.000428

AC:

360

AN:

841948

Other (OTH)

AF:

0.000391

AC:

AN:

46070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000396

AC:

AN:

108488

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

30822

show subpopulations

African (AFR)

AF:

0.000269

AC:

AN:

29737

American (AMR)

AF:

0.00

AC:

AN:

10087

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2613

East Asian (EAS)

AF:

0.000292

AC:

AN:

3429

South Asian (SAS)

AF:

0.00127

AC:

AN:

2360

European-Finnish (FIN)

AF:

0.00106

AC:

AN:

5649

Middle Eastern (MID)

AF:

0.00

AC:

AN:

214

European-Non Finnish (NFE)

AF:

0.000478

AC:

AN:

52248

Other (OTH)

AF:

0.00

AC:

AN:

1471

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000648

Hom.:

Bravo

AF:

0.000321

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.000150

AC:

ExAC

AF:

0.000453

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Focal segmental glomerulosclerosis (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

3.8

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.37

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.69

M_CAP

Pathogenic

0.64

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.86

MutationAssessor

Pathogenic

3.2

PhyloP100

1.9

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-7.5

REVEL

Uncertain

0.34

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Vest4

0.20

MVP

0.78

MPC

1.8

ClinPred

0.16

GERP RS

-0.91

Varity_R

0.23

gMVP

0.76

Mutation Taster

=51/49

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs199849270

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over