Genetic Variant ENSG00000290798:n.1319G>A (chrX-101837615-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000263032.5(ENSG00000290798):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

ENSG00000290798
ENST00000263032.5 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.04

Variant links:

Genes affected

ENSG00000290798 (HGNC:):

ENSG00000290798 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 made for transcript

Verdict is Benign. Variant got -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 id is 2069543.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-101837615-C-T is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
NXF5	NR_028089.1 link	n.1319G>A	non_coding_transcript_exon_variant	Exon 15 of 19
NXF5	NR_159736.1 link	n.1130G>A	non_coding_transcript_exon_variant	Exon 13 of 17
NXF5	NR_159737.1 link	n.1130G>A	non_coding_transcript_exon_variant	Exon 13 of 17

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ENSG00000290798	ENST00000263032.5 link	n.1319G>A	non_coding_transcript_exon_variant	Exon 15 of 19	1
ENSG00000290798	ENST00000332614.6 link	n.1130G>A	non_coding_transcript_exon_variant	Exon 13 of 17	1
ENSG00000290798	ENST00000361330.5 link	n.1130G>A	non_coding_transcript_exon_variant	Exon 13 of 17	1

Frequencies

GnomAD3 genomes

AF:

0.000799

AC:

AN:

111355

Hom.:

Cov.:

AF XY:

0.000358

AC XY:

AN XY:

33555

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

GnomAD3 exomes

AF:

0.000333

AC:

AN:

183360

Hom.:

AF XY:

0.000266

AC XY:

AN XY:

67796

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 SAS 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

Gnomad4 AFR exome

AF:

0.00330

Gnomad4 AMR exome

AF:

0.000341

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000993

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000107

Gnomad4 OTH exome

AF:

0.000434

GnomAD4 genome

AF:

0.000817

AC:

AN:

111411

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

AN XY:

33619

show subpopulations

Gnomad4 AFR

AF:

0.00284

Gnomad4 AMR

AF:

0.000284

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000189

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000111

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 02, 2024

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

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.92

CADD

Benign

4.2

DANN

Benign

0.60

DEOGEN2

Benign

0.0075

T;.

FATHMM_MKL

Benign

0.0029

LIST_S2

Benign

0.43

T;T

M_CAP

Benign

0.0012

MetaRNN

Benign

0.0085

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.2

N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

0.79

N;N

REVEL

Benign

0.015

Sift

Benign

0.15

T;T

Sift4G

Benign

0.45

T;T

Vest4

0.048

MVP

0.43

MPC

0.00093

ClinPred

0.0082

GERP RS

0.79

Varity_R

0.027

gMVP

0.067

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over