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NM_018297.4(NGLY1):c.979G>A (p.Ala327Thr) AND Congenital disorder of deglycosylation

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 28, 2021
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001224579.4

Allele description [Variation Report for NM_018297.4(NGLY1):c.979G>A (p.Ala327Thr)]

NM_018297.4(NGLY1):c.979G>A (p.Ala327Thr)

Gene:
NGLY1:N-glycanase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3p24.2
Genomic location:
Preferred name:
NM_018297.4(NGLY1):c.979G>A (p.Ala327Thr)
HGVS:
  • NC_000003.12:g.25737358C>T
  • NG_034108.1:g.57682G>A
  • NM_001145293.2:c.979G>A
  • NM_001145294.2:c.853G>A
  • NM_001145295.2:c.979G>A
  • NM_018297.4:c.979G>AMANE SELECT
  • NP_001138765.1:p.Ala327Thr
  • NP_001138766.1:p.Ala285Thr
  • NP_001138767.1:p.Ala327Thr
  • NP_060767.2:p.Ala327Thr
  • NC_000003.11:g.25778849C>T
  • NM_018297.3:c.979G>A
Protein change:
A285T
Links:
dbSNP: rs765674070
NCBI 1000 Genomes Browser:
rs765674070
Molecular consequence:
  • NM_001145293.2:c.979G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001145294.2:c.853G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001145295.2:c.979G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_018297.4:c.979G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Congenital disorder of deglycosylation (CDDG)
Identifiers:
MONDO: MONDO:0031376; MedGen: C3808991; OMIM: PS615273

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001396785Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Aug 28, 2021) 		germlineclinical testing

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

Help

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001396785.3

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

Description

This sequence change replaces alanine with threonine at codon 327 of the NGLY1 protein (p.Ala327Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs765674070, ExAC no frequency). This variant has not been reported in the literature in individuals affected with NGLY1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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: Sep 29, 2024