Human Gene Module / Chromosome 15 / GATM

GATMGlycine amidinotransferase (L-arginine:glycine amidinotransferase)

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
0 / 2
Rare Variants / Common Variants
19 / 0
Aliases
GATM, AGAT,  AT,  CCDS3
Associated Syndromes
-
Chromosome Band
15q21.1
Associated Disorders
ID, EP, ASD
Relevance to Autism

An analysis of the clinical, biochemical, and molecular findings in 27 patients with GAMT deficiency determined that 21 of these patients (78%) were autistic, hyperactive, and self-injurious (Mercimek-Mahmutoglu et al., 2006).

Molecular Function

This gene encodes a mitochondrial enzyme that belongs to the amidinotransferase family. This enzyme is involved in creatine biosynthesis, whereby it catalyzes the transfer of a guanido group from L-arginine to glycine, resulting in guanidinoacetic acid, the immediate precursor of creatine. Mutations in this gene cause arginine:glycine amidinotransferase deficiency (also known as cerebral creatine deficiency syndrome 3 (CCDS3) [MIM:612718]), an inborn error of creatine synthesis characterized by mental retardation, language impairment, and behavioral disorders.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
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Reports related to GATM (2 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary GAMT deficiency: features, treatment, and outcome in an inborn error of creatine synthesis Mercimek-Mahmutoglu S , et al. (2006) No ASD, ID, EP
2 Support Creatine Deficiency Syndromes Mercimek-Mahmutoglu S , et al. (2010) No -
Rare Variants   (19)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - frameshift_variant - - Simplex 16855203 Mercimek-Mahmutoglu S , et al. (2006)
c.59G>C - missense_variant - - Simplex 16855203 Mercimek-Mahmutoglu S , et al. (2006)
c.152A>C - missense_variant - - Simplex 16855203 Mercimek-Mahmutoglu S , et al. (2006)
c.327G>A - missense_variant - - Simplex 16855203 Mercimek-Mahmutoglu S , et al. (2006)
c.506G>A - missense_variant - - Simplex 16855203 Mercimek-Mahmutoglu S , et al. (2006)
c.521G>A - missense_variant - - Simplex 16855203 Mercimek-Mahmutoglu S , et al. (2006)
c.590T>C - missense_variant - - Simplex 16855203 Mercimek-Mahmutoglu S , et al. (2006)
c.491dupG - frameshift_variant - - Simplex 16855203 Mercimek-Mahmutoglu S , et al. (2006)
c.526dupG - frameshift_variant - - Simplex 16855203 Mercimek-Mahmutoglu S , et al. (2006)
c.309dup13C - frameshift_variant - - Simplex 16855203 Mercimek-Mahmutoglu S , et al. (2006)
c.571-3G>C - splice_region_variant - - Simplex 16855203 Mercimek-Mahmutoglu S , et al. (2006)
c.327G>A p.Leu109= missense_variant - - Simplex 16855203 Mercimek-Mahmutoglu S , et al. (2006)
c.59G>C - missense_variant Familial Both parents Simplex 16855203 Mercimek-Mahmutoglu S , et al. (2006)
c.160G>C - missense_variant Familial Both parents Simplex 16855203 Mercimek-Mahmutoglu S , et al. (2006)
c.59G>C - missense_variant Familial Both parents Multiplex 16855203 Mercimek-Mahmutoglu S , et al. (2006)
c.491delG - frameshift_variant Familial Both parents Simplex 16855203 Mercimek-Mahmutoglu S , et al. (2006)
c.327G>A p.Leu109= missense_variant - - Simplex and multiplex 16855203 Mercimek-Mahmutoglu S , et al. (2006)
c.64dupG - frameshift_variant Familial Both parents Multiplex 16855203 Mercimek-Mahmutoglu S , et al. (2006)
c.327G>A p.Leu109= missense_variant Familial Both parents Simplex 16855203 Mercimek-Mahmutoglu S , et al. (2006)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

An analysis of the clinical, biochemical, and molecular findings in 27 patients with GAMT deficiency determined that 21 of these patients (78%) were autistic, hyperactive, and self-injurious (Mercimek-Mahmutoglu et al., 2006).

Score Delta: Score remained at S

criteria met
See SFARI Gene'scoring criteria
S

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

10/1/2019
S
icon
S

Score remained at S

New Scoring Scheme
Description

An analysis of the clinical, biochemical, and molecular findings in 27 patients with GAMT deficiency determined that 21 of these patients (78%) were autistic, hyperactive, and self-injurious (Mercimek-Mahmutoglu et al., 2006).

Reports Added
[New Scoring Scheme]
Krishnan Probability Score

Score 0.46041016861573

Ranking 9468/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.86649107678489

Ranking 3494/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.82584560750419

Ranking 2745/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Zhang D Score

Score -0.17596437268318

Ranking 14856/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
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