NM_000045.4(ARG1):c.913G>C (p.Gly305Arg) AND Arginase deficiency

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jul 12, 2022
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:: RCV000664784.12

Allele description [Variation Report for NM_000045.4(ARG1):c.913G>C (p.Gly305Arg)]

NM_000045.4(ARG1):c.913G>C (p.Gly305Arg)

Genes:

ARG1:arginase 1 [Gene - OMIM - HGNC]
MED23:mediator complex subunit 23 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6q23.2

Genomic location:

Preferred name:

NM_000045.4(ARG1):c.913G>C (p.Gly305Arg)

HGVS:

NC_000006.12:g.131583852G>C
NG_007086.2:g.15628G>C
NG_031860.2:g.49372C>G
NM_000045.4:c.913G>CMANE SELECT
NM_001244438.2:c.937G>C
NM_001270521.2:c.4077+3857C>G
NM_001369020.1:c.658G>C
NM_015979.4:c.4095+3857C>G
NP_000036.2:p.Gly305Arg
NP_001231367.1:p.Gly313Arg
NP_001355949.1:p.Gly220Arg
NC_000006.11:g.131904992G>C
NM_000045.3:c.913G>C
NR_160934.1:n.897G>C

Protein change:

G220R

Links:

dbSNP: rs866970619

NCBI 1000 Genomes Browser:

rs866970619

Molecular consequence:

NM_001270521.2:c.4077+3857C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_015979.4:c.4095+3857C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000045.4:c.913G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001244438.2:c.937G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001369020.1:c.658G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_160934.1:n.897G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Arginase deficiency
Synonyms:: ARG1 deficiency; Argininemia
Identifiers:: MONDO: MONDO:0008814; MedGen: C0268548; Orphanet: 90; OMIM: 207800

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000788796	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Uncertain significance (Jan 5, 2017)	unknown	clinical testing	Citation Link,
SCV003470439	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 12, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21310339, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000788796

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Uncertain significance
(Jan 5, 2017)

unknown

clinical testing

Citation Link,

SCV003470439

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 12, 2022)

germline

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Argininemia presenting with progressive spastic diplegia.

Lee BH, Jin HY, Kim GH, Choi JH, Yoo HW.

Pediatr Neurol. 2011 Mar;44(3):218-20. doi: 10.1016/j.pediatrneurol.2010.11.003.

PubMed [citation]

PMID:: 21310339

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 Counsyl, SCV000788796.1

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

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003470439.1

#	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 replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 305 of the ARG1 protein (p.Gly305Arg). This variant is present in population databases (no rsID available, gnomAD 0.004%). This missense change has been observed in individual(s) with ARG1-related conditions (PMID: 21310339). ClinVar contains an entry for this variant (Variation ID: 550134). 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: "Probably Damaging"; Align-GVGD: "Class C15"). 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.

#	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

Last Updated: Oct 20, 2024

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