15-45393893-C-T

Variant names:

• chr15-45393893-C-T
• rs2433610
• ENST00000458245.5:n.640+3029G>A

Variant summary

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

The ENST00000458245.5(GATM):​n.640+3029G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,136 control chromosomes in the GnomAD database, including 4,664 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 0.14 (4664 hom., cov: 32)
• Consequence: GATM ENST00000458245.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229
• Publications: 9 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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Ambry Genetics, G2P
• Fanconi renotubular syndrome 1

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATM	NM_001321015.2	c.-395+3029G>A		intron_variant	Intron 3 of 11		NP_001307944.1
GATM	XM_047432385.1	c.-1057+3029G>A		intron_variant	Intron 3 of 12		XP_047288341.1
GATM	XM_047432386.1	c.31+3029G>A		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.640+3029G>A		intron_variant	Intron 3 of 4	1
GATM	ENST00000561148.5	c.-319+3029G>A		intron_variant	Intron 3 of 4	5		ENSP00000453860.1
GATM	ENST00000527933.2	n.512+2274G>A		intron_variant	Intron 2 of 2	4
GATM	ENST00000560538.1	n.338+3029G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20670 AN: 152018 Hom.: 4634 Cov.: 32

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0406

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00288

Gnomad SAS AF: 0.0555

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.00163

Gnomad OTH AF: 0.0942

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

GnomAD4 genome AF: 0.136 AC: 20743 AN: 152136 Hom.: 4664 Cov.: 32 AF XY: 0.131 AC XY: 9778 AN XY: 74418

African (AFR) AF: 0.471 AC: 19521 AN: 41406

American (AMR) AF: 0.0403 AC: 617 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00250 AC: 13 AN: 5190

South Asian (SAS) AF: 0.0556 AC: 268 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0274 AC: 8 AN: 292

European-Non Finnish (NFE) AF: 0.00163 AC: 111 AN: 68024

Other (OTH) AF: 0.0970 AC: 205 AN: 2114

Alfa AF: 0.0457 Hom.: 2217

Bravo AF: 0.153

Asia WGS AF: 0.0650 AC: 226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	14
DANN	Benign	0.71
PhyloP100		-0.23

Splicing

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

Other links and lift over

dbSNP: rs2433610; hg19: chr15-45686091;