chr15-45361374-C-CTG
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_001482.3(GATM):c.*734_*735insCA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★★).
Frequency
Genomes: 𝑓 0.56 ( 27212 hom., cov: 0)
Exomes 𝑓: 0.67 ( 1 hom. )
Consequence
GATM
NM_001482.3 3_prime_UTR
NM_001482.3 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.32
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 -16 ACMG points.
BP6
?
Variant 15-45361374-C-CTG is Benign according to our data. Variant chr15-45361374-C-CTG is described in ClinVar as [Benign]. Clinvar id is 316203.Status of the report is reviewed_by_expert_panel, 3 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATM | NM_001482.3 | c.*734_*735insCA | 3_prime_UTR_variant | 9/9 | ENST00000396659.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATM | ENST00000396659.8 | c.*734_*735insCA | 3_prime_UTR_variant | 9/9 | 1 | NM_001482.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.559 AC: 84775AN: 151520Hom.: 27157 Cov.: 0
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GnomAD4 exome AF: 0.667 AC: 4AN: 6Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 1AN XY: 2
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GnomAD4 genome ? AF: 0.560 AC: 84893AN: 151636Hom.: 27212 Cov.: 0 AF XY: 0.566 AC XY: 41959AN XY: 74068
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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.*734_*735insCA variant inserts two nucleotides 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 population with >2000 alleles, is 0.8397 (7277/8666 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: 316203). 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 | Jun 14, 2016 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at