rs150246404

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001003722.2(GLE1):c.5C>G(p.Pro2Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000695 in 1,605,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P2P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00080 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00068 ( 0 hom. )

Consequence

GLE1
NM_001003722.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:5B:2

Conservation

PhyloP100: 3.71

Publications

9 publications found

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 Gene-Disease associations (from GenCC):

lethal arthrogryposis-anterior horn cell disease syndrome
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
lethal congenital contracture syndrome 1
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
amyotrophic lateral sclerosis
Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet

GLE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.036649793).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003722.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GLE1	NM_001003722.2	MANE Select	c.5C>G	p.Pro2Arg	missense	Exon 1 of 16	NP_001003722.1	Q53GS7-1
GLE1	NM_001411013.1		c.5C>G	p.Pro2Arg	missense	Exon 1 of 17	NP_001397942.1	A0A804HJ70
GLE1	NM_001499.2		c.5C>G	p.Pro2Arg	missense	Exon 1 of 14	NP_001490.1	B3KMG0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GLE1	ENST00000309971.9	TSL:1 MANE Select	c.5C>G	p.Pro2Arg	missense	Exon 1 of 16	ENSP00000308622.5	Q53GS7-1
GLE1	ENST00000372770.4	TSL:1	c.5C>G	p.Pro2Arg	missense	Exon 1 of 14	ENSP00000361856.4	Q53GS7-2
GLE1	ENST00000898507.1		c.5C>G	p.Pro2Arg	missense	Exon 1 of 17	ENSP00000568566.1

Frequencies

GnomAD3 genomes

AF:

0.000801

AC:

122

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000853

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000991

AC:

249

AN:

251236

AF XY:

0.00110

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00127

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00110

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000684

AC:

994

AN:

1453518

Hom.:

Cov.:

AF XY:

0.000748

AC XY:

541

AN XY:

723686

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33300

American (AMR)

AF:

0.00116

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00107

AC:

AN:

26092

East Asian (EAS)

AF:

0.00

AC:

AN:

39660

South Asian (SAS)

AF:

0.00170

AC:

146

AN:

86084

European-Finnish (FIN)

AF:

0.000263

AC:

AN:

53300

Middle Eastern (MID)

AF:

0.00694

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.000596

AC:

658

AN:

1104498

Other (OTH)

AF:

0.000865

AC:

AN:

60104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

109

164

218

273

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000801

AC:

122

AN:

152338

Hom.:

Cov.:

AF XY:

0.000940

AC XY:

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.0000240

AC:

AN:

41582

American (AMR)

AF:

0.00320

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00186

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000853

AC:

AN:

68022

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000901

Hom.:

Bravo

AF:

0.000873

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00104

AC:

126

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00174

EpiControl

AF:

0.00160

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

GLE1-related disorder (1)

Lethal arthrogryposis-anterior horn cell disease syndrome (1)

Lethal congenital contracture syndrome 1 (1)

Lethal congenital contracture syndrome 1;C5193016:Lethal arthrogryposis-anterior horn cell disease syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.050

Eigen

Benign

0.012

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.77

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.037

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.8

PhyloP100

3.7

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.27

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0040

Polyphen

0.068

Vest4

0.55

MVP

0.78

MPC

2.6

ClinPred

0.13

GERP RS

4.3

PromoterAI

-0.12

Neutral

(source)

Varity_R

0.22

gMVP

0.47

Mutation Taster

=68/32

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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