rs3027589
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The ENST00000218516.4(GLA):c.639+68A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0493 in 615,286 control chromosomes in the GnomAD database, including 891 homozygotes. There are 10,075 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.065 ( 280 hom., 1972 hem., cov: 22)
Exomes 𝑓: 0.046 ( 611 hom. 8103 hem. )
Consequence
GLA
ENST00000218516.4 intron
ENST00000218516.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.129
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 Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant X-101400598-T-C is Benign according to our data. Variant chrX-101400598-T-C is described in ClinVar as [Benign]. Clinvar id is 1275736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GLA | NM_000169.3 | c.639+68A>G | intron_variant | ENST00000218516.4 | NP_000160.1 | |||
RPL36A-HNRNPH2 | NM_001199973.2 | c.300+5141T>C | intron_variant | NP_001186902.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GLA | ENST00000218516.4 | c.639+68A>G | intron_variant | 1 | NM_000169.3 | ENSP00000218516 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0650 AC: 7193AN: 110691Hom.: 279 Cov.: 22 AF XY: 0.0596 AC XY: 1961AN XY: 32923
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GnomAD4 exome AF: 0.0459 AC: 23135AN: 504540Hom.: 611 AF XY: 0.0496 AC XY: 8103AN XY: 163476
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GnomAD4 genome AF: 0.0650 AC: 7204AN: 110746Hom.: 280 Cov.: 22 AF XY: 0.0598 AC XY: 1972AN XY: 32988
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at