ENST00000458245.5:n.208C>A

Variant names:

• chr15-45402120-G-T
• rs3809472
• ENST00000458245.5:n.208C>A

Variant summary

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

The ENST00000458245.5(GATM):​n.208C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 395,098 control chromosomes in the GnomAD database, including 22,815 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 (8863 hom., cov: 33)
  • Exomes 𝑓: 0.30 (13952 hom.)
• Consequence: GATM ENST00000458245.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.520

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]

AFG2B (HGNC:28762): (AFG2 AAA ATPase homolog B) Predicted to enable ATP binding activity. Located in cytoplasm and spindle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFG2B	NM_024063.3	c.-310G>T		upstream_gene_variant		ENST00000305560.11	NP_076968.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATM	ENST00000458245.5	n.208C>A		non_coding_transcript_exon_variant	Exon 1 of 5	1
GATM	ENST00000561148.5	c.-711C>A		5_prime_UTR_variant	Exon 1 of 5	5		ENSP00000453860.1
SPATA5L1	ENST00000305560.11	c.-310G>T		upstream_gene_variant		1	NM_024063.3	ENSP00000305494.6
SPATA5L1	ENST00000559860.2	n.-250G>T		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48499 AN: 152010 Hom.: 8842 Cov.: 33

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.342

GnomAD4 exome AF: 0.304 AC: 73827 AN: 242970 Hom.: 13952 Cov.: 2 AF XY: 0.303 AC XY: 38156 AN XY: 125910

Gnomad4 AFR exome AF: 0.286

Gnomad4 AMR exome AF: 0.518

Gnomad4 ASJ exome AF: 0.333

Gnomad4 EAS exome AF: 0.856

Gnomad4 SAS exome AF: 0.309

Gnomad4 FIN exome AF: 0.290

Gnomad4 NFE exome AF: 0.247

Gnomad4 OTH exome AF: 0.308

GnomAD4 genome AF: 0.319 AC: 48546 AN: 152128 Hom.: 8863 Cov.: 33 AF XY: 0.328 AC XY: 24387 AN XY: 74376

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.831

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.346

Alfa AF: 0.193 Hom.: 529

Bravo AF: 0.337

Asia WGS AF: 0.560 AC: 1945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.9
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3809472; hg19: chr15-45694318;