NM_018297.4(NGLY1):c.1637C>T (p.Ser546Leu) AND Congenital disorder of deglycosylation

Clinical significance:Uncertain significance (Last evaluated: Oct 14, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000651490.5

Allele description [Variation Report for NM_018297.4(NGLY1):c.1637C>T (p.Ser546Leu)]

NM_018297.4(NGLY1):c.1637C>T (p.Ser546Leu)

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.1637C>T (p.Ser546Leu)
HGVS:
  • NC_000003.12:g.25720166G>A
  • NG_034108.1:g.74874C>T
  • NM_001145293.1:c.1583C>T
  • NM_001145294.1:c.1511C>T
  • NM_001145295.1:c.1612-531C>T
  • NM_018297.4:c.1637C>TMANE SELECT
  • NP_001138765.1:p.Ser528Leu
  • NP_001138766.1:p.Ser504Leu
  • NP_060767.2:p.Ser546Leu
  • NC_000003.11:g.25761657G>A
  • NM_018297.3:c.1637C>T
Protein change:
S504L
Links:
dbSNP: rs1040190748
NCBI 1000 Genomes Browser:
rs1040190748
Molecular consequence:
  • NM_001145295.1:c.1612-531C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001145293.1:c.1583C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001145294.1:c.1511C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_018297.4:c.1637C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Congenital disorder of deglycosylation (CDDG)
Synonyms:
CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Iv
Identifiers:
MONDO: MONDO:0014109; MedGen: C3808991; Orphanet: 404454; OMIM: 615273

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000773342Invitaecriteria provided, single submitter
Uncertain significance
(Oct 14, 2020)
germlineclinical testing

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

SCV000897082Fulgent Genetics,Fulgent Geneticscriteria provided, single submitter
Uncertain significance
(Oct 31, 2018)
unknownclinical 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
not providedunknownunknownnot 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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Invitae, SCV000773342.4

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

Description

This sequence change replaces serine with leucine at codon 546 of the NGLY1 protein (p.Ser546Leu). The serine residue is moderately conserved and there is a large physicochemical difference between serine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NGLY1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C1). 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. 5

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

From Fulgent Genetics,Fulgent Genetics, SCV000897082.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 7, 2021

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