NM_000263.4(NAGLU):c.241A>G (p.Thr81Ala) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Jun 25, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001244118.1

Allele description [Variation Report for NM_000263.4(NAGLU):c.241A>G (p.Thr81Ala)]

NM_000263.4(NAGLU):c.241A>G (p.Thr81Ala)

Gene:
NAGLU:N-acetyl-alpha-glucosaminidase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.2
Genomic location:
Preferred name:
NM_000263.4(NAGLU):c.241A>G (p.Thr81Ala)
HGVS:
  • NC_000017.11:g.42536513A>G
  • NG_011552.1:g.5581A>G
  • NM_000263.4:c.241A>GMANE SELECT
  • NP_000254.2:p.Thr81Ala
  • NC_000017.10:g.40688531A>G
  • NM_000263.3:c.241A>G
Protein change:
T81A
Links:
dbSNP: rs2092906625
NCBI 1000 Genomes Browser:
rs2092906625
Molecular consequence:
  • NM_000263.4:c.241A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Mucopolysaccharidosis, MPS-III-B (MPS3B)
Synonyms:
NAGLU DEFICIENCY; Mucopoly-saccharidosis type 3B; Sanfilippo syndrome B; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009656; MedGen: C0086648; OMIM: 252920
Name:
Charcot-Marie-Tooth disease, axonal type 2V (CMT2V)
Synonyms:
CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 2V; CHARCOT-MARIE-TOOTH DISEASE, AXONAL, AUTOSOMAL DOMINANT, TYPE 2V
Identifiers:
MONDO: MONDO:0014665; MedGen: C4225306; Orphanet: 447964; OMIM: 616491

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001417318Invitaecriteria provided, single submitter
Uncertain significance
(Jun 25, 2019)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

A rapid and sensitive method for measuring N-acetylglucosaminidase activity in cultured cells.

Mauri V, Lotfi P, Segatori L, Sardiello M.

PLoS One. 2013 Jun 28;8(6):e68060. doi: 10.1371/journal.pone.0068060. Print 2013.

PubMed [citation]
PMID:
23840811
PMCID:
PMC3695942

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, SCV001417318.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces threonine with alanine at codon 81 of the NAGLU protein (p.Thr81Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has been observed in an individual with mucopolysaccharidosis type III (PMID: 23840811). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Nov 27, 2021

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