15-45361509-T-C
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
The NM_001482.3(GATM):c.*600A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 154,360 control chromosomes in the GnomAD database, including 9,029 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).
Frequency
Genomes: 𝑓 0.32 ( 8903 hom., cov: 32)
Exomes 𝑓: 0.30 ( 126 hom. )
Consequence
GATM
NM_001482.3 3_prime_UTR
NM_001482.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.85
Genes affected
GATM (HGNC:4175): (glycine amidinotransferase) 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, an inborn error of creatine synthesis characterized by cognitive disability, language impairment, and behavioral disorders. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -18 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
Variant 15-45361509-T-C is Benign according to our data. Variant chr15-45361509-T-C is described in ClinVar as [Benign]. Clinvar id is 316206.Status of the report is reviewed_by_expert_panel, 3 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATM | NM_001482.3 | c.*600A>G | 3_prime_UTR_variant | 9/9 | ENST00000396659.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATM | ENST00000396659.8 | c.*600A>G | 3_prime_UTR_variant | 9/9 | 1 | NM_001482.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.320 AC: 48623AN: 151944Hom.: 8881 Cov.: 32
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GnomAD4 exome AF: 0.295 AC: 678AN: 2298Hom.: 126 Cov.: 0 AF XY: 0.307 AC XY: 362AN XY: 1178
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GnomAD4 genome ? AF: 0.320 AC: 48670AN: 152062Hom.: 8903 Cov.: 32 AF XY: 0.329 AC XY: 24439AN XY: 74324
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Arginine:glycine amidinotransferase deficiency Benign:2
Benign, reviewed by expert panel | curation | ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel, ClinGen | Jun 06, 2022 | The NM_001482.3:c.*600A>G variant is a single nucleotide substitution in the 3'UTR of GATM. Because the variant is located in the 3'UTR, it is not expected to alter the amino acid sequence. The highest population minor allele frequency in gnomAD v2.1.1, in a continental population with >2000 alleles, is 0.2934 (2554/8704 alleles) in the African population, which is higher than the ClinGen CCDS VCEP’s threshold for BA1 (>0.0005), and therefore meets this criterion (BA1). There is a ClinVar entry for this variant (Variation ID: 316206). In summary, this variant meets the criteria to be classified as benign for AGAT deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel (Specifications Version 1.1.0): BA1. (Classification approved by the ClinGen CCDS VCEP on June 6, 2022). - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at