NM_024063.3:c.-18C>T

Variant names:

• chr15-45402412-C-T
• rs1365610
• NM_024063.3:c.-18C>T

Variant summary

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

The NM_024063.3(AFG2B):​c.-18C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 1,578,396 control chromosomes in the GnomAD database, including 79,495 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 (8942 hom., cov: 33)
  • Exomes 𝑓: 0.29 (70553 hom.)
• Consequence: AFG2B NM_024063.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36
• Publications: 24 publications found

Genes affected

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]

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: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, ClinGen
• 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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024063.3. 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
	AFG2B	NM_024063.3	MANE Select	c.-18C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	NP_076968.2	Q9BVQ7-1
	AFG2B	NM_024063.3	MANE Select	c.-18C>T		5_prime_UTR	Exon 1 of 8	NP_076968.2	Q9BVQ7-1
	AFG2B	NM_001323640.2		c.-18C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	NP_001310569.1	Q9BVQ7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFG2B	ENST00000305560.11	TSL:1 MANE Select	c.-18C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000305494.6	Q9BVQ7-1
	AFG2B	ENST00000305560.11	TSL:1 MANE Select	c.-18C>T		5_prime_UTR	Exon 1 of 8	ENSP00000305494.6	Q9BVQ7-1
	AFG2B	ENST00000907461.1		c.-18C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000577520.1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48817 AN: 152036 Hom.: 8921 Cov.: 33

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.344

GnomAD2 exomes AF: 0.367 AC: 79531 AN: 216806 AF XY: 0.354

Gnomad AFR exome AF: 0.304

Gnomad AMR exome AF: 0.630

Gnomad ASJ exome AF: 0.348

Gnomad EAS exome AF: 0.821

Gnomad FIN exome AF: 0.310

Gnomad NFE exome AF: 0.264

Gnomad OTH exome AF: 0.344

GnomAD4 exome AF: 0.293 AC: 418304 AN: 1426242 Hom.: 70553 Cov.: 34 AF XY: 0.294 AC XY: 208307 AN XY: 708984

African (AFR) AF: 0.302 AC: 9035 AN: 29888

American (AMR) AF: 0.607 AC: 21885 AN: 36030

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 8513 AN: 24654

East Asian (EAS) AF: 0.844 AC: 31112 AN: 36844

South Asian (SAS) AF: 0.341 AC: 27897 AN: 81862

European-Finnish (FIN) AF: 0.307 AC: 16304 AN: 53152

Middle Eastern (MID) AF: 0.334 AC: 1901 AN: 5684

European-Non Finnish (NFE) AF: 0.258 AC: 283098 AN: 1099284

Other (OTH) AF: 0.315 AC: 18559 AN: 58844

GnomAD4 genome AF: 0.321 AC: 48865 AN: 152154 Hom.: 8942 Cov.: 33 AF XY: 0.330 AC XY: 24536 AN XY: 74386

African (AFR) AF: 0.304 AC: 12635 AN: 41542

American (AMR) AF: 0.475 AC: 7268 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1201 AN: 3470

East Asian (EAS) AF: 0.830 AC: 4272 AN: 5144

South Asian (SAS) AF: 0.351 AC: 1693 AN: 4830

European-Finnish (FIN) AF: 0.309 AC: 3268 AN: 10588

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17550 AN: 67970

Other (OTH) AF: 0.348 AC: 735 AN: 2112

Alfa AF: 0.286 Hom.: 3236

Bravo AF: 0.340

Asia WGS AF: 0.561 AC: 1949 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.8
DANN	Benign	0.74
PhyloP100		-2.4
PromoterAI		-0.018	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1365610; hg19: chr15-45694610; COSMIC: COSV107369192; COSMIC: COSV107369192;