NM_153006.3(NAGS):c.739C>T (p.Gln247Ter) AND Hyperammonemia, type III

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Mar 10, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001381890.8

Allele description [Variation Report for NM_153006.3(NAGS):c.739C>T (p.Gln247Ter)]

NM_153006.3(NAGS):c.739C>T (p.Gln247Ter)

Gene:

NAGS:N-acetylglutamate synthase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.31

Genomic location:

Preferred name:

NM_153006.3(NAGS):c.739C>T (p.Gln247Ter)

HGVS:

NC_000017.11:g.44006061C>T
NG_008106.1:g.6398C>T
NG_023338.1:g.3409G>A
NM_153006.3:c.739C>TMANE SELECT
NP_694551.1:p.Gln247Ter
NC_000017.10:g.42083429C>T

Protein change:

Q247*

Links:

dbSNP: rs748875458

NCBI 1000 Genomes Browser:

rs748875458

Molecular consequence:

NM_153006.3:c.739C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hyperammonemia, type III (NAGSD)
Synonyms:: NAG synthetase deficiency; Hyperammonemia due to N-acetylglutamate synthase deficiency
Identifiers:: MONDO: MONDO:0009377; MedGen: C0268543; Orphanet: 927; OMIM: 237310

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Mus musculus neural cell adhesion molecule 1 (Ncam1), transcript variant 2, mRNA
Mus musculus neural cell adhesion molecule 1 (Ncam1), transcript variant 2, mRNA
gi|2222724958|ref|NM_010875.4|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001580464	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 5, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12594532, 28492532
SCV002810933	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 1, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004199448	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 10, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001580464

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 5, 2023)

germline

clinical testing

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

SCV002810933

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 1, 2022)

unknown

clinical testing

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

SCV004199448

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 10, 2024)

unknown

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Null mutations in the N-acetylglutamate synthase gene associated with acute neonatal disease and hyperammonemia.

Caldovic L, Morizono H, Panglao MG, Cheng SF, Packman S, Tuchman M.

Hum Genet. 2003 Apr;112(4):364-8. Epub 2003 Feb 20.

PubMed [citation]

PMID:: 12594532

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

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001580464.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Gln247*) in the NAGS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NAGS are known to be pathogenic (PMID: 12594532). This variant is present in population databases (rs748875458, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with NAGS-related conditions. ClinVar contains an entry for this variant (Variation ID: 1069900). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Fulgent Genetics, Fulgent Genetics, SCV002810933.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004199448.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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