15-45380831-T-C

Variant names:

• chr15-45380831-T-C
• rs1346268
• ENST00000458245.5:n.641-272A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321015.2(GATM):​c.-394-272A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 151,898 control chromosomes in the GnomAD database, including 8,868 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. The gene GATM is included in the ClinGen Criteria Specification Registry.

• Frequency: Genomes: 𝑓 0.32 (8868 hom., cov: 31)
• Consequence: GATM NM_001321015.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.440
• Publications: 29 publications found

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]

GATM Gene-Disease associations (from GenCC):

• AGAT deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, ClinGen
• Fanconi renotubular syndrome 1

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• primary Fanconi syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000275672 (HGNC:):

ACMG classification

Specifications for GATM are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321015.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATM	NM_001321015.2		c.-394-272A>G		intron	N/A	NP_001307944.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATM	ENST00000458245.5	TSL:1	n.641-272A>G		intron	N/A
	GATM	ENST00000561148.5	TSL:5	c.-318-4012A>G		intron	N/A	ENSP00000453860.1	H0YN43
	GATM	ENST00000527933.2	TSL:4	n.513-272A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48568 AN: 151780 Hom.: 8846 Cov.: 31

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.832

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.341

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.320 AC: 48615 AN: 151898 Hom.: 8868 Cov.: 31 AF XY: 0.329 AC XY: 24397 AN XY: 74226

African (AFR) AF: 0.297 AC: 12304 AN: 41410

American (AMR) AF: 0.474 AC: 7228 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1228 AN: 3470

East Asian (EAS) AF: 0.833 AC: 4306 AN: 5172

South Asian (SAS) AF: 0.350 AC: 1686 AN: 4814

European-Finnish (FIN) AF: 0.308 AC: 3241 AN: 10510

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17649 AN: 67952

Other (OTH) AF: 0.345 AC: 728 AN: 2110

Alfa AF: 0.300 Hom.: 18266

Bravo AF: 0.338

Asia WGS AF: 0.561 AC: 1948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.2
DANN	Benign	0.59
PhyloP100		0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1346268; hg19: chr15-45673029;