Genetic Variant NXF5:n.1319G>A (chrX-101837615-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000263032.5(NXF5):n.1319G>A 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 0.000184 in 1,209,572 control chromosomes in the GnomAD database, including 1 homozygotes. There are 51 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00082 ( 0 hom., 14 hem., cov: 22)

Exomes 𝑓: 0.00012 ( 1 hom. 37 hem. )

Consequence

NXF5
ENST00000263032.5 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.04

Publications

3 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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008513838).

BP6

Variant X-101837615-C-T is Benign according to our data. Variant chrX-101837615-C-T is described in ClinVar as Benign. ClinVar VariationId is 2069543.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 14 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.1319G>A	non_coding_transcript_exon	Exon 15 of 19
NXF5	NR_159736.1	n.1130G>A	non_coding_transcript_exon	Exon 13 of 17
NXF5	NR_159737.1	n.1130G>A	non_coding_transcript_exon	Exon 13 of 17

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
NXF5	ENST00000263032.5	TSL:1	n.1319G>A	non_coding_transcript_exon	Exon 15 of 19
NXF5	ENST00000332614.6	TSL:1	n.1130G>A	non_coding_transcript_exon	Exon 13 of 17
NXF5	ENST00000361330.5	TSL:1	n.1130G>A	non_coding_transcript_exon	Exon 13 of 17

Frequencies

GnomAD3 genomes

AF:

0.000799

AC:

AN:

111355

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00278

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000284

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000333

AC:

AN:

183360

AF XY:

0.000266

show subpopulations

Gnomad AFR exome

AF:

0.00365

Gnomad AMR exome

AF:

0.000438

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000119

AC:

131

AN:

1098161

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

363521

show subpopulations

African (AFR)

AF:

0.00330

AC:

AN:

26402

American (AMR)

AF:

0.000341

AC:

AN:

35201

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19383

East Asian (EAS)

AF:

0.0000993

AC:

AN:

30205

South Asian (SAS)

AF:

0.00

AC:

AN:

54135

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40532

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.0000107

AC:

AN:

842071

Other (OTH)

AF:

0.000434

AC:

AN:

46096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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:

0.000817

AC:

AN:

111411

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

AN XY:

33619

show subpopulations

African (AFR)

AF:

0.00284

AC:

AN:

30641

American (AMR)

AF:

0.000284

AC:

AN:

10572

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2639

East Asian (EAS)

AF:

0.00

AC:

AN:

3511

South Asian (SAS)

AF:

0.00

AC:

AN:

2619

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5968

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

53045

Other (OTH)

AF:

0.00

AC:

AN:

1519

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.000288

Hom.:

Bravo

AF:

0.00107

ESP6500AA

AF:

0.00391

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000346

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Benign

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

0.075

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.92

CADD

Benign

4.2

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.0075

FATHMM_MKL

Benign

0.0029

LIST_S2

Benign

0.43

M_CAP

Benign

0.0012

MetaRNN

Benign

0.0085

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.2

PhyloP100

1.0

PrimateAI

Benign

0.39

PROVEAN

Benign

0.79

REVEL

Benign

0.015

Sift

Benign

0.15

Sift4G

Benign

0.45

Vest4

0.048

MVP

0.43

MPC

0.00093

ClinPred

0.0082

GERP RS

0.79

Varity_R

0.027

gMVP

0.067

Mutation Taster

=100/0

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

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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