Variant chrX-109535925-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000218004.5(NXT2):c.43G>C(p.Gly15Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000475 in 1,205,160 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 212 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., 18 hem., cov: 23)

Exomes 𝑓: 0.00046 ( 0 hom. 194 hem. )

Consequence

NXT2
ENST00000218004.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0570

Variant links:

Genes affected

NXT2 (HGNC:18151): (nuclear transport factor 2 like export factor 2) The protein encoded by this gene contains a nuclear transport factor 2 (NTF2) domain, which plays an important role in the trafficking of macromolecules, ions, and small molecules between the cytoplasm and nucleus. This protein may also have a role in mRNA nuclear export. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jun 2011]

NXT2 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=0.004984081).

BP6

Variant X-109535925-G-C is Benign according to our data. Variant chrX-109535925-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2661179.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 18 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NXT2	NM_018698.5 linkuse as main transcript	c.43G>C	p.Gly15Arg	missense_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NXT2	ENST00000218004.5 linkuse as main transcript	c.43G>C	p.Gly15Arg	missense_variant	1/5	1			Q9NPJ8-3

Frequencies

GnomAD3 genomes

AF:

0.000599

AC:

AN:

111761

Hom.:

Cov.:

AF XY:

0.000530

AC XY:

AN XY:

33939

show subpopulations

Gnomad AFR

AF:

0.0000326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00227

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000831

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000997

Gnomad OTH

AF:

0.00134

GnomAD3 exomes

AF:

0.000454

AC:

AN:

178600

Hom.:

AF XY:

0.000411

AC XY:

AN XY:

63262

show subpopulations

Gnomad AFR exome

AF:

0.0000777

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00148

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00107

Gnomad NFE exome

AF:

0.000628

Gnomad OTH exome

AF:

0.000455

GnomAD4 exome

AF:

0.000463

AC:

506

AN:

1093346

Hom.:

Cov.:

AF XY:

0.000540

AC XY:

194

AN XY:

358984

show subpopulations

Gnomad4 AFR exome

AF:

0.0000760

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00197

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00136

Gnomad4 NFE exome

AF:

0.000473

Gnomad4 OTH exome

AF:

0.000283

GnomAD4 genome

AF:

0.000599

AC:

AN:

111814

Hom.:

Cov.:

AF XY:

0.000529

AC XY:

AN XY:

34002

show subpopulations

Gnomad4 AFR

AF:

0.0000325

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00227

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000831

Gnomad4 NFE

AF:

0.000997

Gnomad4 OTH

AF:

0.00132

Alfa

AF:

0.000915

Hom.:

Bravo

AF:

0.000416

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.000437

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

NXT2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.012

DANN

Benign

0.17

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.30

M_CAP

Benign

0.00082

MetaRNN

Benign

0.0050

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.18

REVEL

Benign

0.011

Sift

Benign

0.86

Sift4G

Benign

0.86

Polyphen

0.0

Vest4

0.088

MutPred

0.14

Gain of helix (P = 0.0143);

MVP

0.043

MPC

0.042

ClinPred

0.0084

GERP RS

-5.4

gMVP

0.090

Splicing

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