15-45402520-C-T

Variant names:

• chr15-45402520-C-T
• rs775705935
• NM_024063.3:c.91C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_024063.3(AFG2B):​c.91C>T​(p.Leu31Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,451,652 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: AFG2B NM_024063.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106
• Publications: 1 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP7: Synonymous conserved (PhyloP=0.106 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.91C>T	p.Leu31Leu	synonymous	Exon 1 of 8	NP_076968.2	Q9BVQ7-1
	AFG2B	NM_001323640.2		c.91C>T	p.Leu31Leu	synonymous	Exon 1 of 5	NP_001310569.1	Q9BVQ7-2
	AFG2B	NR_027635.2		n.185C>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.91C>T	p.Leu31Leu	synonymous	Exon 1 of 8	ENSP00000305494.6	Q9BVQ7-1
	AFG2B	ENST00000907461.1		c.91C>T	p.Leu31Leu	synonymous	Exon 1 of 8	ENSP00000577520.1
	AFG2B	ENST00000960280.1		c.91C>T	p.Leu31Leu	synonymous	Exon 1 of 8	ENSP00000630339.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000620 AC: 9 AN: 1451652 Hom.: 0 Cov.: 33 AF XY: 0.00000831 AC XY: 6 AN XY: 721604

African (AFR) AF: 0.00 AC: 0 AN: 33040

American (AMR) AF: 0.00 AC: 0 AN: 42772

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25862

East Asian (EAS) AF: 0.000180 AC: 7 AN: 38970

South Asian (SAS) AF: 0.00 AC: 0 AN: 85290

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52138

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1107884

Other (OTH) AF: 0.00 AC: 0 AN: 59944

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	12
DANN	Benign	0.95
PhyloP100		0.11
PromoterAI		-0.0090	Neutral

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: rs775705935; hg19: chr15-45694718;