9-128504855-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001003722.2(GLE1):​c.50C>T​(p.Ser17Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

GLE1
NM_001003722.2 missense

Scores

1
15
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.79
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GLE1NM_001003722.2 linkc.50C>T p.Ser17Phe missense_variant Exon 1 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.50C>T p.Ser17Phe missense_variant Exon 1 of 16 1 NM_001003722.2 ENSP00000308622.5 Q53GS7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Jan 21, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.50C>T (p.S17F) alteration is located in exon 1 (coding exon 1) of the GLE1 gene. This alteration results from a C to T substitution at nucleotide position 50, causing the serine (S) at amino acid position 17 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.61
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
-0.070
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.19
T;.
Eigen
Uncertain
0.33
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.85
T;T
M_CAP
Uncertain
0.23
D
MetaRNN
Uncertain
0.69
D;D
MetaSVM
Uncertain
0.16
D
MutationAssessor
Uncertain
2.7
M;M
PrimateAI
Uncertain
0.66
T
PROVEAN
Uncertain
-2.8
D;D
REVEL
Uncertain
0.40
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.0020
D;D
Polyphen
0.98
D;D
Vest4
0.76
MutPred
0.33
Loss of disorder (P = 0.0024);Loss of disorder (P = 0.0024);
MVP
0.86
MPC
2.6
ClinPred
0.99
D
GERP RS
4.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.53
gMVP
0.80

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: chr9-131267134; API