15-45402570-G-T

Variant names:

• chr15-45402570-G-T
• rs1834686
• NM_024063.3:c.141G>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_024063.3(AFG2B):​c.141G>T​(p.Val47Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0245 in 1,579,392 control chromosomes in the GnomAD database, including 6,954 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (3644 hom., cov: 33)
  • Exomes 𝑓: 0.014 (3310 hom.)
• Consequence: AFG2B NM_024063.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.994
• Publications: 3 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 15-45402570-G-T is Benign according to our data. Variant chr15-45402570-G-T is described in ClinVar as Benign. ClinVar VariationId is 1235297.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.994 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.409 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.141G>T	p.Val47Val	synonymous	Exon 1 of 8	NP_076968.2	Q9BVQ7-1
	AFG2B	NM_001323640.2		c.141G>T	p.Val47Val	synonymous	Exon 1 of 5	NP_001310569.1	Q9BVQ7-2
	AFG2B	NR_027635.2		n.235G>T		non_coding_transcript_exon	Exon 1 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFG2B	ENST00000305560.11	TSL:1 MANE Select	c.141G>T	p.Val47Val	synonymous	Exon 1 of 8	ENSP00000305494.6	Q9BVQ7-1
	AFG2B	ENST00000907461.1		c.141G>T	p.Val47Val	synonymous	Exon 1 of 8	ENSP00000577520.1
	AFG2B	ENST00000960280.1		c.141G>T	p.Val47Val	synonymous	Exon 1 of 8	ENSP00000630339.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18132 AN: 152126 Hom.: 3617 Cov.: 33

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0332

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0488

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00113

Gnomad OTH AF: 0.0817

GnomAD2 exomes AF: 0.0316 AC: 5759 AN: 182076 AF XY: 0.0278

Gnomad AFR exome AF: 0.432

Gnomad AMR exome AF: 0.0129

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00180

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000590

Gnomad OTH exome AF: 0.0132

GnomAD4 exome AF: 0.0144 AC: 20546 AN: 1427148 Hom.: 3310 Cov.: 33 AF XY: 0.0139 AC XY: 9859 AN XY: 707752

African (AFR) AF: 0.432 AC: 13988 AN: 32378

American (AMR) AF: 0.0164 AC: 642 AN: 39180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25530

East Asian (EAS) AF: 0.000996 AC: 37 AN: 37154

South Asian (SAS) AF: 0.0424 AC: 3523 AN: 83082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48132

Middle Eastern (MID) AF: 0.0187 AC: 107 AN: 5722

European-Non Finnish (NFE) AF: 0.000439 AC: 481 AN: 1096864

Other (OTH) AF: 0.0299 AC: 1768 AN: 59106

GnomAD4 genome AF: 0.120 AC: 18202 AN: 152244 Hom.: 3644 Cov.: 33 AF XY: 0.115 AC XY: 8598 AN XY: 74448

African (AFR) AF: 0.414 AC: 17189 AN: 41504

American (AMR) AF: 0.0329 AC: 504 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5170

South Asian (SAS) AF: 0.0488 AC: 236 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.00113 AC: 77 AN: 68014

Other (OTH) AF: 0.0847 AC: 179 AN: 2114

Alfa AF: 0.0396 Hom.: 753

Bravo AF: 0.134

Asia WGS AF: 0.0580 AC: 201 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	12
DANN	Benign	0.85
PhyloP100		0.99
PromoterAI		-0.038	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1834686; hg19: chr15-45694768;