chr15-45402549-C-T

Variant names:

• chr15-45402549-C-T
• rs375506384
• NM_024063.3:c.120C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6 BP7

The NM_024063.3(AFG2B):​c.120C>T​(p.Gly40Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000144 in 1,590,550 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00014 (1 hom.)
• Consequence: AFG2B NM_024063.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.11
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 15-45402549-C-T is Benign according to our data. Variant chr15-45402549-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3042678.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.12 with no splicing effect.

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.120C>T	p.Gly40Gly	synonymous	Exon 1 of 8	NP_076968.2	Q9BVQ7-1
	AFG2B	NM_001323640.2		c.120C>T	p.Gly40Gly	synonymous	Exon 1 of 5	NP_001310569.1	Q9BVQ7-2
	AFG2B	NR_027635.2		n.214C>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.120C>T	p.Gly40Gly	synonymous	Exon 1 of 8	ENSP00000305494.6	Q9BVQ7-1
	AFG2B	ENST00000907461.1		c.120C>T	p.Gly40Gly	synonymous	Exon 1 of 8	ENSP00000577520.1
	AFG2B	ENST00000960280.1		c.120C>T	p.Gly40Gly	synonymous	Exon 1 of 8	ENSP00000630339.1

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 152240 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000286 AC: 57 AN: 199536 AF XY: 0.000292

Gnomad AFR exome AF: 0.0000914

Gnomad AMR exome AF: 0.000103

Gnomad ASJ exome AF: 0.00289

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000105

Gnomad OTH exome AF: 0.000388

GnomAD4 exome AF: 0.000140 AC: 201 AN: 1438192 Hom.: 1 Cov.: 33 AF XY: 0.000158 AC XY: 113 AN XY: 714070

African (AFR) AF: 0.0000610 AC: 2 AN: 32766

American (AMR) AF: 0.0000740 AC: 3 AN: 40528

Ashkenazi Jewish (ASJ) AF: 0.00218 AC: 56 AN: 25662

East Asian (EAS) AF: 0.0000264 AC: 1 AN: 37904

South Asian (SAS) AF: 0.000476 AC: 40 AN: 84108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50206

Middle Eastern (MID) AF: 0.00157 AC: 9 AN: 5732

European-Non Finnish (NFE) AF: 0.0000653 AC: 72 AN: 1101774

Other (OTH) AF: 0.000302 AC: 18 AN: 59512

GnomAD4 genome AF: 0.000184 AC: 28 AN: 152358 Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14 AN XY: 74512

African (AFR) AF: 0.0000240 AC: 1 AN: 41596

American (AMR) AF: 0.000131 AC: 2 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4834

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68032

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000426 Hom.: 0

Bravo AF: 0.000155

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	AFG2B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	13
DANN	Benign	0.93
PhyloP100		-1.1
PromoterAI		-0.014	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs375506384; hg19: chr15-45694747;