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NM_000169.3(GLA):c.1102G>A (p.Ala368Thr)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(1);Uncertain significance(4)

Review status:
criteria provided, conflicting interpretations
Submissions:
6 (Most recent: May 26, 2021)
Last evaluated:
Oct 9, 2020
Accession:
VCV000042451.7
Variation ID:
42451
Description:
single nucleotide variant
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NM_000169.3(GLA):c.1102G>A (p.Ala368Thr)

Allele ID
51621
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
Xq22.1
Genomic location
X: 101397997 (GRCh38) GRCh38 UCSC
X: 100652985 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000023.10:g.100652985C>T
NC_000023.11:g.101397997C>T
NM_000169.3:c.1102G>A MANE Select NP_000160.1:p.Ala368Thr missense
... more HGVS
Protein change
A368T
Other names
-
Canonical SPDI
NC_000023.11:101397996:C:T
Functional consequence
effect on protein activity [Variation Ontology VariO:0053]
Global minor allele frequency (GMAF)
0.00053 (T)

Allele frequency
1000 Genomes Project 0.00053
Trans-Omics for Precision Medicine (TOPMed) 0.00041
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00019
Links
ClinGen: CA021399
dbSNP: rs144994244
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 3 criteria provided, multiple submitters, no conflicts Oct 9, 2020 RCV000463728.7
Uncertain significance 1 criteria provided, single submitter Jul 8, 2019 RCV001507537.1
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Apr 8, 2015 RCV000035300.3
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
GLA Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
11 860
RPL36A-HNRNPH2 - - - GRCh38
GRCh37
- 865

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely benign
(Apr 08, 2015)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
GeneDx
Accession: SCV000513155.4
Submitted: (Mar 26, 2018)
Evidence details
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
Uncertain significance
(Jul 06, 2012)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000058948.5
Submitted: (Mar 21, 2019)
Evidence details
Comment:
Variant classified as Uncertain Significance - Favor Benign. The Ala368Thr varia nt in GLA has been identified in 2/3835 African American chromosomes from a broa … (more)
Uncertain significance
(Jul 08, 2019)
criteria provided, single submitter
Method: clinical testing
Not provided
Allele origin: germline
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001713142.1
Submitted: (May 26, 2021)
Evidence details
Uncertain significance
(Dec 05, 2018)
criteria provided, single submitter
Method: clinical testing
Fabry disease
Allele origin: germline
Color Health, Inc
Accession: SCV001360072.1
Submitted: (May 19, 2020)
Comment:
Variant of Uncertain Significance due to insufficient evidence: This missense variant replaces alanine with threonine at codon 368 of the GLA protein. Computational prediction tools … (more)
Evidence details
Uncertain significance
(Oct 09, 2020)
criteria provided, single submitter
Method: clinical testing
Fabry disease
Allele origin: germline
Invitae
Accession: SCV000543777.6
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (3)
Comment:
This sequence change replaces alanine with threonine at codon 368 of the GLA protein (p.Ala368Thr). The alanine residue is weakly conserved and there is a … (more)
Likely benign
(Jan 22, 2020)
no assertion criteria provided
Method: curation
Fabry disease
(X-linked inheritance)
Allele origin: germline
Broad Institute Rare Disease Group, Broad Institute
Accession: SCV001422795.1
Submitted: (Mar 09, 2020)
Comment:
X-linked inheritance (primarily recessive with milder female expression)
Evidence details
Publications
PubMed (3)
Other databases
https://erepo.clinicalgenome.org…
Comment:
The p.Ala368Thr variant in GLA has been reported in 1 African American female with Fabry Disease (PMID: 24503780), and has been identified in 0.1% (19/18974) … (more)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Targeted Screening of Fabry Disease in Male Hemodialysis Patients in Brazil Highlights Importance of Family Screening. Silva CA Nephron 2016 PMID: 27576502
The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing. Pugh TJ Genetics in medicine : official journal of the American College of Medical Genetics 2014 PMID: 24503780
Lysosome-associated protein 1 (LAMP-1) and lysosome-associated protein 2 (LAMP-2) in a larger family carrier of Fabry disease. Pereira EM Gene 2014 PMID: 24334114
Functional characterisation of alpha-galactosidase a mutations as a basis for a new classification system in fabry disease. Lukas J PLoS genetics 2013 PMID: 23935525
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/48697a7a-16bd-4245-afe6-f3350a8bf880 - - - -

Text-mined citations for rs144994244...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jul 07, 2021