rs3027585
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000169.3(GLA):c.-12G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0423 in 1,200,657 control chromosomes in the GnomAD database, including 1,251 homozygotes. There are 16,901 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.066 ( 281 hom., 2123 hem., cov: 23)
Exomes 𝑓: 0.040 ( 970 hom. 14778 hem. )
Consequence
GLA
NM_000169.3 5_prime_UTR
NM_000169.3 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.576
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
?
Variant X-101407915-C-T is Benign according to our data. Variant chrX-101407915-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 42449.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-101407915-C-T is described in Lovd as [Benign]. Variant chrX-101407915-C-T is described in Lovd as [Likely_benign].
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 | UniProt |
---|---|---|---|---|---|---|---|
GLA | NM_000169.3 | c.-12G>A | 5_prime_UTR_variant | 1/7 | ENST00000218516.4 | ||
RPL36A-HNRNPH2 | NM_001199973.2 | c.301-4021C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLA | ENST00000218516.4 | c.-12G>A | 5_prime_UTR_variant | 1/7 | 1 | NM_000169.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0658 AC: 7361AN: 111875Hom.: 280 Cov.: 23 AF XY: 0.0619 AC XY: 2110AN XY: 34069
GnomAD3 genomes
?
AF:
AC:
7361
AN:
111875
Hom.:
Cov.:
23
AF XY:
AC XY:
2110
AN XY:
34069
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0607 AC: 11095AN: 182916Hom.: 411 AF XY: 0.0577 AC XY: 3895AN XY: 67450
GnomAD3 exomes
AF:
AC:
11095
AN:
182916
Hom.:
AF XY:
AC XY:
3895
AN XY:
67450
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0398 AC: 43354AN: 1088727Hom.: 970 Cov.: 30 AF XY: 0.0417 AC XY: 14778AN XY: 354697
GnomAD4 exome
AF:
AC:
43354
AN:
1088727
Hom.:
Cov.:
30
AF XY:
AC XY:
14778
AN XY:
354697
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0659 AC: 7374AN: 111930Hom.: 281 Cov.: 23 AF XY: 0.0622 AC XY: 2123AN XY: 34134
GnomAD4 genome
?
AF:
AC:
7374
AN:
111930
Hom.:
Cov.:
23
AF XY:
AC XY:
2123
AN XY:
34134
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:14
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:6
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 17, 2012 | -12G>A in the 5' UTR of GLA: This variant is not expected to have clinical signi ficance because it has been identified in 14.5% (467/3216) of African American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS/; dbSNP rs3027585) - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 11, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Fabry disease Benign:4
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 19, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 19, 2018 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
not provided Benign:3
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Dec 30, 2016 | - - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | This variant is associated with the following publications: (PMID: 25772321) - |
Hypertrophic cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at