rs2433610

Positions:

• chr15-45393893-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321015.2(GATM):​c.-395+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 NM_001321015.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229

Genes affected

GATM (HGNC:):

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=-0.75).
• 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/exons	MANE	Protein	UniProt
GATM	NM_001321015.2	c.-395+3029G>A		intron_variant			NP_001307944.1
GATM	XM_047432385.1	c.-1057+3029G>A		intron_variant			XP_047288341.1
GATM	XM_047432386.1	c.31+3029G>A		intron_variant			XP_047288342.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATM	ENST00000458245.5	n.640+3029G>A		intron_variant		1
GATM	ENST00000561148.5	c.-319+3029G>A		intron_variant		5		ENSP00000453860.1
GATM	ENST00000527933.2	n.512+2274G>A		intron_variant		4
GATM	ENST00000560538.1	n.338+3029G>A		intron_variant		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

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.0403

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00250

Gnomad4 SAS AF: 0.0556

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00163

Gnomad4 OTH AF: 0.0970

Alfa AF: 0.110 Hom.: 415

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2433610; hg19: chr15-45686091;