dbSNP rs145904413: NXF5:n.1358A>G (chrX-101837576-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The ENST00000263032.5(NXF5):n.1358A>G variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.0000182 in 1,210,335 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., 9 hem., cov: 22)

Exomes 𝑓: 0.0000082 ( 0 hom. 1 hem. )

Consequence

NXF5
ENST00000263032.5 non_coding_transcript_exon

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.46

Publications

0 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 -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.866

BS2

High Hemizygotes in GnomAd4 at 9 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.1358A>G	non_coding_transcript_exon	Exon 15 of 19
NXF5	NR_159736.1	n.1169A>G	non_coding_transcript_exon	Exon 13 of 17
NXF5	NR_159737.1	n.1169A>G	non_coding_transcript_exon	Exon 13 of 17

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
NXF5	ENST00000263032.5	TSL:1	n.1358A>G	non_coding_transcript_exon	Exon 15 of 19
NXF5	ENST00000332614.6	TSL:1	n.1169A>G	non_coding_transcript_exon	Exon 13 of 17
NXF5	ENST00000361330.5	TSL:1	n.1169A>G	non_coding_transcript_exon	Exon 13 of 17

Frequencies

GnomAD3 genomes

AF:

0.000116

AC:

AN:

112085

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000422

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000327

AC:

AN:

183500

AF XY:

0.0000294

show subpopulations

Gnomad AFR exome

AF:

0.000456

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000819

AC:

AN:

1098250

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363604

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

26403

American (AMR)

AF:

0.00

AC:

AN:

35207

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19386

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.00

AC:

AN:

54149

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40534

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

842130

Other (OTH)

AF:

0.0000434

AC:

AN:

46098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.000116

AC:

AN:

112085

Hom.:

Cov.:

AF XY:

0.000263

AC XY:

AN XY:

34259

show subpopulations

African (AFR)

AF:

0.000422

AC:

AN:

30837

American (AMR)

AF:

0.00

AC:

AN:

10663

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2654

East Asian (EAS)

AF:

0.00

AC:

AN:

3538

South Asian (SAS)

AF:

0.00

AC:

AN:

2674

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6115

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53174

Other (OTH)

AF:

0.00

AC:

AN:

1505

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.563

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:

0.0000617

Hom.:

Bravo

AF:

0.000208

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.037

BayesDel_noAF

Pathogenic

0.14

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Uncertain

0.42

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.78

M_CAP

Benign

0.068

MetaRNN

Pathogenic

0.87

MetaSVM

Uncertain

-0.18

MutationAssessor

Pathogenic

3.0

PhyloP100

5.5

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-7.9

REVEL

Uncertain

0.62

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.76

MVP

0.88

MPC

0.0011

ClinPred

0.35

GERP RS

2.1

Varity_R

0.89

gMVP

0.74

Mutation Taster

=97/3

polymorphism

(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

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

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

Computational scores

Splicing

Publications

Other links and lift over