15-45380831-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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.

• 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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATM	NM_001321015.2	c.-394-272A>G		intron_variant	Intron 3 of 11		NP_001307944.1
GATM	XM_047432385.1	c.-1056-272A>G		intron_variant	Intron 3 of 12		XP_047288341.1
GATM	XM_047432386.1	c.32-262A>G		intron_variant	Intron 3 of 11		XP_047288342.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATM	ENST00000458245.5	n.641-272A>G		intron_variant	Intron 3 of 4	1
GATM	ENST00000561148.5	c.-318-4012A>G		intron_variant	Intron 3 of 4	5		ENSP00000453860.1
GATM	ENST00000527933.2	n.513-272A>G		intron_variant	Intron 2 of 2	4
GATM	ENST00000560538.1	n.339-4012A>G		intron_variant	Intron 1 of 1	3

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

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.833

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.345

Alfa AF: 0.294 Hom.: 5134

Bravo AF: 0.338

Asia WGS AF: 0.561 AC: 1948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1346268; hg19: chr15-45673029;