NM_001003722.2:c.1849G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PM5BP4

The NM_001003722.2(GLE1):​c.1849G>T​(p.Val617Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V617M) has been classified as Pathogenic.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GLE1
NM_001003722.2 missense

Scores

10
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.43
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr9-128538058-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 6464.Status of the report is criteria_provided_single_submitter, 1 stars.
BP4
Computational evidence support a benign effect (MetaRNN=0.42082134).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GLE1NM_001003722.2 linkc.1849G>T p.Val617Leu missense_variant Exon 13 of 16 ENST00000309971.9 NP_001003722.1 Q53GS7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GLE1ENST00000309971.9 linkc.1849G>T p.Val617Leu missense_variant Exon 13 of 16 1 NM_001003722.2 ENSP00000308622.5 Q53GS7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1457164
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
725242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.03e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.46
BayesDel_addAF
Benign
-0.057
T
BayesDel_noAF
Benign
-0.32
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.19
T;.
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.040
D
MetaRNN
Benign
0.42
T;T
MetaSVM
Benign
-0.37
T
MutationAssessor
Benign
1.6
L;L
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-1.4
N;N
REVEL
Uncertain
0.30
Sift
Uncertain
0.012
D;D
Sift4G
Uncertain
0.044
D;D
Polyphen
0.98
D;P
Vest4
0.34
MutPred
0.57
Loss of catalytic residue at V617 (P = 0.1747);Loss of catalytic residue at V617 (P = 0.1747);
MVP
0.70
MPC
0.80
ClinPred
0.88
D
GERP RS
4.8
Varity_R
0.34
gMVP
0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-131300337; API