NM_000404.4(GLB1):c.1634dup (p.Asn545fs) AND multiple conditions

Clinical significance:Pathogenic (Last evaluated: Apr 22, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001380450.1

Allele description [Variation Report for NM_000404.4(GLB1):c.1634dup (p.Asn545fs)]

NM_000404.4(GLB1):c.1634dup (p.Asn545fs)

Gene:
GLB1:galactosidase beta 1 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
3p22.3
Genomic location:
Preferred name:
NM_000404.4(GLB1):c.1634dup (p.Asn545fs)
HGVS:
  • NC_000003.12:g.33014157dup
  • NG_009005.1:g.88047dup
  • NM_000404.4:c.1634dupMANE SELECT
  • NM_001079811.3:c.1544dup
  • NM_001135602.3:c.1241dup
  • NM_001317040.2:c.1778dup
  • NM_001393580.1:c.1634dup
  • NP_000395.3:p.Asn545fs
  • NP_001073279.2:p.Asn515fs
  • NP_001129074.2:p.Asn414fs
  • NP_001303969.2:p.Asn593fs
  • NP_001380509.1:p.Asn545fs
  • NC_000003.11:g.33055647_33055648insT
  • NC_000003.11:g.33055649dup
  • NM_000404.2:c.1634dupA
Protein change:
N414fs
Links:
dbSNP: rs754131566
NCBI 1000 Genomes Browser:
rs754131566
Molecular consequence:
  • NM_000404.4:c.1634dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001079811.3:c.1544dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001135602.3:c.1241dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001317040.2:c.1778dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001393580.1:c.1634dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Mucopolysaccharidosis, MPS-IV-B (MPS4B)
Synonyms:
MPS IVB; Morquio syndrome B; MPS 4B; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009660; MedGen: C0086652; Orphanet: 582; OMIM: 253010
Name:
GM1 gangliosidosis
Synonyms:
Beta galactosidase 1 deficiency; GLB 1 deficiency
Identifiers:
MONDO: MONDO:0018149; MedGen: C0085131

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001578531Invitaecriteria provided, single submitter
Pathogenic
(Apr 22, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001578531.1

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

Description

This sequence change results in a premature translational stop signal in the GLB1 gene (p.Asn545Lysfs*40). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 134 amino acids of the GLB1 protein. This variant is present in population databases (rs754131566, ExAC 0.001%). This variant has not been reported in the literature in individuals with GLB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 550413). This variant disrupts the C-terminus of the GLB1 protein. Other variant(s) that disrupt this region (p.Asp564Argfs*21) have been determined to be pathogenic (Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 24, 2021

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