rs2275260

Positions:

chr9-128523676-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001003722.2(GLE1):c.727A>G(p.Ile243Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,613,590 control chromosomes in the GnomAD database, including 47,049 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6241 hom., cov: 31)

Exomes 𝑓: 0.23 ( 40808 hom. )

Consequence

GLE1
NM_001003722.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 1.81

Variant links:

Genes affected

GLE1 (HGNC:4315): (GLE1 RNA export mediator) This gene encodes a predicted 75-kDa polypeptide with high sequence and structure homology to yeast Gle1p, which is nuclear protein with a leucine-rich nuclear export sequence essential for poly(A)+RNA export. Inhibition of human GLE1L by microinjection of antibodies against GLE1L in HeLa cells resulted in inhibition of poly(A)+RNA export. Immunoflourescence studies show that GLE1L is localized at the nuclear pore complexes. This localization suggests that GLE1L may act at a terminal step in the export of mature RNA messages to the cytoplasm. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GLE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.893707E-4).

BP6

Variant 9-128523676-A-G is Benign according to our data. Variant chr9-128523676-A-G is described in ClinVar as [Benign]. Clinvar id is 198109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128523676-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLE1	NM_001003722.2 linkuse as main transcript	c.727A>G	p.Ile243Val	missense_variant	6/16	ENST00000309971.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLE1	ENST00000309971.9 linkuse as main transcript	c.727A>G	p.Ile243Val	missense_variant	6/16	1	NM_001003722.2	P1	Q53GS7-1

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

41216

AN:

151816

Hom.:

6231

Cov.:

show subpopulations

Gnomad AFR

AF:

0.377

Gnomad AMI

AF:

0.150

Gnomad AMR

AF:

0.258

Gnomad ASJ

AF:

0.162

Gnomad EAS

AF:

0.466

Gnomad SAS

AF:

0.340

Gnomad FIN

AF:

0.253

Gnomad MID

AF:

0.245

Gnomad NFE

AF:

0.202

Gnomad OTH

AF:

0.255

GnomAD3 exomes

AF:

0.267

AC:

67017

AN:

251016

Hom.:

9775

AF XY:

0.264

AC XY:

35878

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.388

Gnomad AMR exome

AF:

0.308

Gnomad ASJ exome

AF:

0.168

Gnomad EAS exome

AF:

0.441

Gnomad SAS exome

AF:

0.324

Gnomad FIN exome

AF:

0.244

Gnomad NFE exome

AF:

0.209

Gnomad OTH exome

AF:

0.235

GnomAD4 exome

AF:

0.227

AC:

331476

AN:

1461656

Hom.:

40808

Cov.:

AF XY:

0.229

AC XY:

166274

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.388

Gnomad4 AMR exome

AF:

0.300

Gnomad4 ASJ exome

AF:

0.167

Gnomad4 EAS exome

AF:

0.478

Gnomad4 SAS exome

AF:

0.315

Gnomad4 FIN exome

AF:

0.236

Gnomad4 NFE exome

AF:

0.203

Gnomad4 OTH exome

AF:

0.240

GnomAD4 genome

AF:

0.272

AC:

41257

AN:

151934

Hom.:

6241

Cov.:

AF XY:

0.276

AC XY:

20493

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.376

Gnomad4 AMR

AF:

0.257

Gnomad4 ASJ

AF:

0.162

Gnomad4 EAS

AF:

0.466

Gnomad4 SAS

AF:

0.341

Gnomad4 FIN

AF:

0.253

Gnomad4 NFE

AF:

0.202

Gnomad4 OTH

AF:

0.255

Alfa

AF:

0.222

Hom.:

8174

Bravo

AF:

0.281

TwinsUK

AF:

0.197

AC:

731

ALSPAC

AF:

0.205

AC:

789

ESP6500AA

AF:

0.388

AC:

1711

ESP6500EA

AF:

0.201

AC:

1732

ExAC

AF:

0.267

AC:

32374

Asia WGS

AF:

0.424

AC:

1472

AN:

3478

EpiCase

AF:

0.202

EpiControl

AF:

0.205

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 05, 2015	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 27884173, 23421748) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Lethal arthrogryposis-anterior horn cell disease syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -

Lethal congenital contracture syndrome 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -

Lethal congenital contractural syndrome Finnish type

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Nov 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

4.8

DANN

Benign

0.54

DEOGEN2

Benign

0.0053

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.086

T;T

MetaRNN

Benign

0.00059

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.0

N;N

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.27

PROVEAN

Benign

0.53

N;N

REVEL

Benign

0.23

Sift

Benign

0.11

T;T

Sift4G

Benign

0.37

T;T

Polyphen

0.0

B;B

Vest4

0.0050

MPC

0.18

ClinPred

0.0033

GERP RS

-2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.019

gMVP

0.040

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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