NM_054012.4(ASS1):c.970G>A (p.Gly324Ser) AND Citrullinemia

Clinical significance:Pathogenic (Last evaluated: Sep 28, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001376631.1

Allele description [Variation Report for NM_054012.4(ASS1):c.970G>A (p.Gly324Ser)]

NM_054012.4(ASS1):c.970G>A (p.Gly324Ser)

Gene:
ASS1:argininosuccinate synthase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q34.11
Genomic location:
Preferred name:
NM_054012.4(ASS1):c.970G>A (p.Gly324Ser)
HGVS:
  • NC_000009.12:g.130489464G>A
  • NG_011542.1:g.49758G>A
  • NM_000050.4:c.970G>A
  • NM_054012.4:c.970G>AMANE SELECT
  • NP_000041.2:p.Gly324Ser
  • NP_446464.1:p.Gly324Ser
  • NC_000009.11:g.133364851G>A
Protein change:
G324S; GLY324SER
Links:
OMIM: 603470.0007; dbSNP: rs121908639
NCBI 1000 Genomes Browser:
rs121908639
Molecular consequence:
  • NM_000050.4:c.970G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_054012.4:c.970G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Citrullinemia (CTNL1)
Identifiers:
MONDO: MONDO:0015991; MedGen: C0175683

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000630068Invitaecriteria provided, single submitter
Pathogenic
(Sep 28, 2020)
germlineclinical testing

PubMed (8)
[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

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]
PMID:
17576681
PMCID:
PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]
PMID:
9536098
See all PubMed Citations (8)

Details of each submission

From Invitae, SCV000630068.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

This sequence change replaces glycine with serine at codon 324 of the ASS1 protein (p.Gly324Ser). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and serine. This variant also falls at the last nucleotide of exon 13 of the ASS1 coding sequence, which is part of the consensus splice site for this exon. Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). This variant is present in population databases (rs121908639, ExAC 0.02%). This variant has been reported as homozygous or in combination with another ASS1 variant in individuals affected with citrullinemia (PMID: 12815590, 2358466, 11211875, 18473344, 14680976). ClinVar contains an entry for this variant (Variation ID: 6327). 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 C0). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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 7, 2021

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