chr15-45362082-G-C
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1
The NM_001482.3(GATM):c.*27C>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 0.000663 in 1,402,906 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).
Frequency
Genomes: 𝑓 0.00052 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00068 ( 0 hom. )
Consequence
GATM
NM_001482.3 3_prime_UTR
NM_001482.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.57
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.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 15-45362082-G-C is Benign according to our data. Variant chr15-45362082-G-C is described in ClinVar as [Benign]. Clinvar id is 316209.Status of the report is reviewed_by_expert_panel, 3 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000519 (79/152256) while in subpopulation NFE AF= 0.000912 (62/68012). AF 95% confidence interval is 0.000729. There are 1 homozygotes in gnomad4. There are 36 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATM | NM_001482.3 | c.*27C>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.*27C>G | 3_prime_UTR_variant | 9/9 | 1 | NM_001482.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000519 AC: 79AN: 152138Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000471 AC: 118AN: 250420Hom.: 0 AF XY: 0.000458 AC XY: 62AN XY: 135454
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ClinVar
Significance: Benign
Submissions summary: Uncertain:1Benign:1
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Arginine:glycine amidinotransferase deficiency Uncertain:1Benign:1
Benign, reviewed by expert panel | curation | ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel, ClinGen | Jun 06, 2022 | The NM_001482.3:c.*27C>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 is 0.000856 (110/128560 alleles) in the non-Finnish European 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: 316209). 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). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance 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