Genetic Variant NXF5:n.1382A>G (chrX-101837552-T-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6BS2

The ENST00000263032.5(NXF5):n.1382A>G variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.000125 in 1,210,506 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 54 hemizygotes in GnomAD. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., 7 hem., cov: 23)

Exomes 𝑓: 0.00012 ( 0 hom. 47 hem. )

Consequence

NXF5
ENST00000263032.5 non_coding_transcript_exon

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 7.13

Publications

1 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.

BP6

Variant X-101837552-T-C is Benign according to our data. Variant chrX-101837552-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 2366999.

BS2

High Hemizygotes in GnomAd4 at 7 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.1382A>G	non_coding_transcript_exon	Exon 15 of 19
NXF5	NR_159736.1	n.1193A>G	non_coding_transcript_exon	Exon 13 of 17
NXF5	NR_159737.1	n.1193A>G	non_coding_transcript_exon	Exon 13 of 17

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
NXF5	ENST00000263032.5	TSL:1	n.1382A>G	non_coding_transcript_exon	Exon 15 of 19
NXF5	ENST00000332614.6	TSL:1	n.1193A>G	non_coding_transcript_exon	Exon 13 of 17
NXF5	ENST00000361330.5	TSL:1	n.1193A>G	non_coding_transcript_exon	Exon 13 of 17

Frequencies

GnomAD3 genomes

AF:

0.000160

AC:

AN:

112256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000281

Gnomad ASJ

AF:

0.00452

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000564

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000245

AC:

AN:

183489

AF XY:

0.000162

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000437

Gnomad ASJ exome

AF:

0.00387

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.000662

GnomAD4 exome

AF:

0.000121

AC:

133

AN:

1098250

Hom.:

Cov.:

AF XY:

0.000129

AC XY:

AN XY:

363604

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26403

American (AMR)

AF:

0.000369

AC:

AN:

35207

Ashkenazi Jewish (ASJ)

AF:

0.00495

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:

0.0000119

AC:

AN:

842130

Other (OTH)

AF:

0.000304

AC:

AN:

46098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

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:

0.000160

AC:

AN:

112256

Hom.:

Cov.:

AF XY:

0.000203

AC XY:

AN XY:

34444

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30861

American (AMR)

AF:

0.000281

AC:

AN:

10681

Ashkenazi Jewish (ASJ)

AF:

0.00452

AC:

AN:

2655

East Asian (EAS)

AF:

0.00

AC:

AN:

3557

South Asian (SAS)

AF:

0.00

AC:

AN:

2676

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6177

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000564

AC:

AN:

53206

Other (OTH)

AF:

0.00

AC:

AN:

1516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

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:

0.000181

Hom.:

Bravo

AF:

0.000189

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.000165

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Pathogenic

0.26

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.42

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.076

MetaRNN

Uncertain

0.45

MetaSVM

Benign

-0.28

MutationAssessor

Pathogenic

3.0

PhyloP100

7.1

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-6.7

REVEL

Uncertain

0.56

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0060

Vest4

0.86

MVP

0.83

MPC

0.0011

ClinPred

0.50

GERP RS

2.1

Varity_R

0.62

gMVP

0.72

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over