chrX-101397809-TTAAAG-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_000169.3(GLA):c.1285_1289del(p.Leu429LysfsTer?) variant causes a frameshift, stop lost 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: 23)
Exomes 𝑓: 9.3e-7 ( 0 hom. 1 hem. )
Failed GnomAD Quality Control
Consequence
GLA
NM_000169.3 frameshift, stop_lost
NM_000169.3 frameshift, stop_lost
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.71
Genes affected
GLA (HGNC:4296): (galactosidase alpha) This gene encodes a homodimeric glycoprotein that hydrolyses the terminal alpha-galactosyl moieties from glycolipids and glycoproteins. This enzyme predominantly hydrolyzes ceramide trihexoside, and it can catalyze the hydrolysis of melibiose into galactose and glucose. A variety of mutations in this gene affect the synthesis, processing, and stability of this enzyme, which causes Fabry disease, a rare lysosomal storage disorder that results from a failure to catabolize alpha-D-galactosyl glycolipid moieties. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Frameshift in the end of transcript resulting in stoplost. Downstream stopcodon found after 428 codons.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLA | NM_000169.3 | c.1285_1289del | p.Leu429LysfsTer? | frameshift_variant, stop_lost | 7/7 | ENST00000218516.4 | |
RPL36A-HNRNPH2 | NM_001199973.2 | c.300+2356_300+2360del | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLA | ENST00000218516.4 | c.1285_1289del | p.Leu429LysfsTer? | frameshift_variant, stop_lost | 7/7 | 1 | NM_000169.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.27e-7 AC: 1AN: 1078723Hom.: 0 AF XY: 0.00000289 AC XY: 1AN XY: 345727
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
1078723
Hom.:
AF XY:
AC XY:
1
AN XY:
345727
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 01, 2022 | The c.1285_1289delCTTTA variant, located in coding exon 7 of the GLA gene, results from a deletion of 5 nucleotides at nucleotide positions 1285 to 1289, causing a translational frameshift with a predicted alternate stop codon (p.L429Kfs*?). This alteration occurs at the 3' terminus of theGLA gene, is not expected to trigger nonsense-mediated mRNAdecay and results in the elongation of the protein. This frameshift impacts the lastamino acid of the native protein. The exact functional effect of the altered amino acids is unknown. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
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Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.