chr15-45402120-G-T

Variant names:

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

Variant summary

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

The NM_001321015.2(GATM):​c.-827C>A variant causes a 5 prime UTR 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 NM_001321015.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.520
• Publications: 19 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]

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]

AFG2B Gene-Disease associations (from GenCC):

• hearing loss, autosomal recessive 119

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen
• neurodevelopmental disorder with hearing loss and spasticity

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -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.

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.-827C>A		5_prime_UTR	Exon 1 of 12	NP_001307944.1
	AFG2B	NM_024063.3	MANE Select	c.-310G>T		upstream_gene	N/A	NP_076968.2	Q9BVQ7-1
	AFG2B	NM_001323640.2		c.-310G>T		upstream_gene	N/A	NP_001310569.1	Q9BVQ7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATM	ENST00000458245.5	TSL:1	n.208C>A		non_coding_transcript_exon	Exon 1 of 5
	GATM	ENST00000561148.5	TSL:5	c.-711C>A		5_prime_UTR	Exon 1 of 5	ENSP00000453860.1	H0YN43
	AFG2B	ENST00000305560.11	TSL:1 MANE Select	c.-310G>T		upstream_gene	N/A	ENSP00000305494.6	Q9BVQ7-1

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

African (AFR) AF: 0.286 AC: 1617 AN: 5658

American (AMR) AF: 0.518 AC: 2661 AN: 5142

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 2729 AN: 8206

East Asian (EAS) AF: 0.856 AC: 11673 AN: 13636

South Asian (SAS) AF: 0.309 AC: 6689 AN: 21642

European-Finnish (FIN) AF: 0.290 AC: 5365 AN: 18486

Middle Eastern (MID) AF: 0.310 AC: 375 AN: 1210

European-Non Finnish (NFE) AF: 0.247 AC: 37926 AN: 153422

Other (OTH) AF: 0.308 AC: 4792 AN: 15568

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

African (AFR) AF: 0.296 AC: 12293 AN: 41492

American (AMR) AF: 0.474 AC: 7252 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1203 AN: 3470

East Asian (EAS) AF: 0.831 AC: 4306 AN: 5180

South Asian (SAS) AF: 0.351 AC: 1693 AN: 4824

European-Finnish (FIN) AF: 0.309 AC: 3266 AN: 10570

Middle Eastern (MID) AF: 0.277 AC: 81 AN: 292

European-Non Finnish (NFE) AF: 0.258 AC: 17559 AN: 67988

Other (OTH) AF: 0.346 AC: 730 AN: 2110

Alfa AF: 0.198 Hom.: 568

Bravo AF: 0.337

Asia WGS AF: 0.560 AC: 1945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.9
DANN	Benign	0.73
PhyloP100		-0.52
PromoterAI		0.018	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3809472; hg19: chr15-45694318;