15-45402120-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001321015.2(GATM):​c.-827C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. The gene GATM is included in the ClinGen Criteria Specification Registry.

• Frequency: Genomes: not found (cov: 33)
• 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

Specifications for GATM are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

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>G		5_prime_UTR	Exon 1 of 12	NP_001307944.1
	AFG2B	NM_024063.3	MANE Select	c.-310G>C		upstream_gene	N/A	NP_076968.2	Q9BVQ7-1
	AFG2B	NM_001323640.2		c.-310G>C		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>G		non_coding_transcript_exon	Exon 1 of 5
	GATM	ENST00000561148.5	TSL:5	c.-711C>G		5_prime_UTR	Exon 1 of 5	ENSP00000453860.1	H0YN43
	AFG2B	ENST00000305560.11	TSL:1 MANE Select	c.-310G>C		upstream_gene	N/A	ENSP00000305494.6	Q9BVQ7-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 2

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 568

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.4
DANN	Benign	0.67
PhyloP100		-0.52
PromoterAI		0.021	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;