NM_000045.4(ARG1):c.93del (p.Arg32fs) AND Arginase deficiency

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 11, 2023
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:: RCV001390418.15

Allele description [Variation Report for NM_000045.4(ARG1):c.93del (p.Arg32fs)]

NM_000045.4(ARG1):c.93del (p.Arg32fs)

Genes:

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

Variant type:

Deletion

Cytogenetic location:

6q23.2

Genomic location:

Preferred name:

NM_000045.4(ARG1):c.93del (p.Arg32fs)

HGVS:

NC_000006.12:g.131576698del
NG_007086.2:g.8474del
NG_031860.2:g.56526del
NM_000045.4:c.93delMANE SELECT
NM_001244438.2:c.93del
NM_001270521.2:c.4078-2403del
NM_001369020.1:c.93del
NM_015979.4:c.4096-2403del
NP_000036.2:p.Arg32fs
NP_001231367.1:p.Arg32fs
NP_001355949.1:p.Arg32fs
NC_000006.11:g.131897838del

Protein change:

R32fs

Links:

dbSNP: rs755975244

NCBI 1000 Genomes Browser:

rs755975244

Molecular consequence:

NM_000045.4:c.93del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001244438.2:c.93del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369020.1:c.93del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001270521.2:c.4078-2403del - intron variant - [Sequence Ontology: SO:0001627]
NM_015979.4:c.4096-2403del - intron variant - [Sequence Ontology: SO:0001627]

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
SCV001592149	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 11, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 19936428, 7649538, 12052859, 28492532
SCV004208660	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 15, 2022)	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

SCV001592149

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 11, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV004208660

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 15, 2022)

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

A novel mutation in ARG1 gene is responsible for arginase deficiency in an Asian family.

Hertecant JL, Al-Gazali LI, Karuvantevida NS, Ali BR.

Saudi Med J. 2009 Dec;30(12):1601-3.

PubMed [citation]

PMID:: 19936428

Molecular basis of phenotypic variation in patients with argininemia.

Uchino T, Snyderman SE, Lambert M, Qureshi IA, Shapira SK, Sansaricq C, Smit LM, Jakobs C, Matsuda I.

Hum Genet. 1995 Sep;96(3):255-60.

PubMed [citation]

PMID:: 7649538

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001592149.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1076486). This premature translational stop signal has been observed in individual(s) with arginase deficiency (PMID: 19936428). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs755975244, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Arg32Glufs*16) in the ARG1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ARG1 are known to be pathogenic (PMID: 7649538, 12052859).

#	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 Baylor Genetics, SCV004208660.1

#	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

Last Updated: Apr 15, 2024

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