rs386833693
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_001003722.2(GLE1):c.433-10A>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 29)
Exomes 𝑓: 0.0000022 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
GLE1
NM_001003722.2 splice_polypyrimidine_tract, intron
NM_001003722.2 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0001725
2
Clinical Significance
Conservation
PhyloP100: 0.0570
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 Benign. Variant got -10 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
?
Variant 9-128522658-A-C is Benign according to our data. Variant chr9-128522658-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1561616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLE1 | NM_001003722.2 | c.433-10A>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000309971.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLE1 | ENST00000309971.9 | c.433-10A>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001003722.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 29
GnomAD3 genomes
?
Cov.:
29
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000216 AC: 3AN: 1385912Hom.: 0 Cov.: 38 AF XY: 0.00000290 AC XY: 2AN XY: 689272
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
3
AN:
1385912
Hom.:
Cov.:
38
AF XY:
AC XY:
2
AN XY:
689272
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 29
GnomAD4 genome
?
Cov.:
29
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 26, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at