NM_000169.3(GLA):c.1102G>A (p.Ala368Thr) AND not specified

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Apr 8, 2015)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000035300.3

Allele description [Variation Report for NM_000169.3(GLA):c.1102G>A (p.Ala368Thr)]

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

Genes:
RPL36A-HNRNPH2:RPL36A-HNRNPH2 readthrough [Gene - HGNC]
GLA:galactosidase alpha [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq22.1
Genomic location:
Preferred name:
NM_000169.3(GLA):c.1102G>A (p.Ala368Thr)
HGVS:
  • NC_000023.11:g.101397997C>T
  • NG_007119.1:g.14967G>A
  • NM_000169.2:c.1102G>A
  • NM_000169.3:c.1102G>AMANE SELECT
  • NM_001199973.2:c.300+2540C>T
  • NM_001199974.2:c.177+6175C>T
  • NP_000160.1:p.Ala368Thr
  • NP_000160.1:p.Ala368Thr
  • LRG_672t1:c.1102G>A
  • LRG_672:g.14967G>A
  • NC_000023.10:g.100652985C>T
  • NM_000169.2(GLA):c.1102G>A
  • NR_164783.1:n.1181G>A
  • c.1102G>A
  • p.A368T
Protein change:
A368T
Links:
dbSNP: rs144994244
NCBI 1000 Genomes Browser:
rs144994244
Molecular consequence:
  • NM_001199973.2:c.300+2540C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001199974.2:c.177+6175C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000169.2:c.1102G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000169.3:c.1102G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_164783.1:n.1181G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Functional consequence:
effect on protein activity [Variation Ontology: 0053]
Observations:
1

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000058948Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Uncertain significance
(Jul 6, 2012)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV000513155GeneDxcriteria provided, single submitter
Likely benign
(Apr 8, 2015)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot provided11not providednot providednot providedclinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV000058948.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

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 d population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu /EVS). Alanine (Ala) at position 368 is not conserved in mammals with other spec ies carrying various other amino acid residues and 1 species (atlantic salmon) c arries a threonine (Thr; this variant), suggesting that this change may be toler ated. In addition, computational analyses (biochemical amino acid properties, Al ignGVGD, PolyPhen2, and SIFT) suggest that this variant may not impact the prote in, though this information is not predictive enough to rule out pathogenicity. In summary, the frequency of this variant and lack of amino acid conservation su ggests that it may be more likely benign, but additional information is needed t o fully assess its clinical significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

From GeneDx, SCV000513155.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

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 a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 7, 2021

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