NM_001079524.2(PAICS):c.158A>G (p.Lys53Arg) AND Phosphoribosylaminoimidazole carboxylase deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 28, 2022
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV002248317.1

Allele description [Variation Report for NM_001079524.2(PAICS):c.158A>G (p.Lys53Arg)]

NM_001079524.2(PAICS):c.158A>G (p.Lys53Arg)

Gene:

PAICS:phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q12

Genomic location:

Preferred name:

NM_001079524.2(PAICS):c.158A>G (p.Lys53Arg)

Other names:

PAICS, LYS53ARG (rs192831239)

HGVS:

NC_000004.12:g.56441804A>G
NM_001079524.2:c.158A>GMANE SELECT
NM_001079525.2:c.158A>G
NM_001392010.1:c.1304A>G
NM_001392011.1:c.1220A>G
NM_001392012.1:c.785A>G
NM_006452.4:c.158A>G
NP_001072992.1:p.Lys53Arg
NP_001072993.1:p.Lys53Arg
NP_001378939.1:p.Lys435Arg
NP_001378940.1:p.Lys407Arg
NP_001378941.1:p.Lys262Arg
NP_006443.1:p.Lys53Arg
NC_000004.11:g.57307970A>G
NM_001079525.1:c.158A>G

Protein change:

K262R; LYS53ARG

Links:

OMIM: 172439.0001; dbSNP: rs192831239

NCBI 1000 Genomes Browser:

rs192831239

Molecular consequence:

NM_001079524.2:c.158A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001079525.2:c.158A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001392010.1:c.1304A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001392011.1:c.1220A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001392012.1:c.785A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_006452.4:c.158A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Phosphoribosylaminoimidazole carboxylase deficiency (PAICSD)
Identifiers:: MONDO: MONDO:0859244; MedGen: C1291561; OMIM: 619859

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002520388	OMIM	no assertion criteria provided	Pathogenic (Apr 28, 2022)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002520388

OMIM

no assertion criteria provided

Pathogenic
(Apr 28, 2022)

germline

literature only

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

PAICS deficiency, a new defect of de novo purine synthesis resulting in multiple congenital anomalies and fatal outcome.

Pelet A, Skopova V, Steuerwald U, Baresova V, Zarhrate M, Plaza JM, Hnizda A, Krijt M, Souckova O, Wibrand F, Andorsdóttir G, Joensen F, Sedlak D, Bleyer AJ, Kmoch S, Lyonnet S, Zikanova M.

Hum Mol Genet. 2019 Nov 15;28(22):3805-3814. doi: 10.1093/hmg/ddz237.

PubMed [citation]

PMID:: 31600779

Details of each submission

From OMIM, SCV002520388.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 2 sibs from the Faroe Islands with phosphoribosylaminoimidazole carboxylase deficiency (PAICSD; 619859), who were born to consanguineous parents, Pelet et al. (2019) identified homozygosity for a c.158A-G transition (c.158A-G, NM_001079525.1) in exon 2 of the PAICS gene, resulting in a lys53-to-arg (K53R) substitution. The mutation, which was identified by whole-exome sequencing and confirmed by Sanger sequencing, was present in heterozygous state in the parents. The mutation was present in gnomAD at an allele frequency of 0.001 in non-Finnish Europeans, 0.0002 in Africans, and 0.0007 in Latinos. Molecular modeling predicted that the mutation resulted in destabilization of the PAICS enzyme pocket. PAICS enzyme activity was reduced to 10% in patient fibroblasts and to 50% in fibroblasts from the heterozygous parents and a heterozygous sib compared to controls.

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

Last Updated: Dec 24, 2023

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