rs2279651

Positions:

• chr5-35039332-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_031900.4(AGXT2):​c.354T>C​(p.His118=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 1,612,958 control chromosomes in the GnomAD database, including 256,644 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 0.52 (21152 hom., cov: 32)
  • Exomes 𝑓: 0.56 (235492 hom.)
• Consequence: AGXT2 NM_031900.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.32

Genes affected

AGXT2 (HGNC:14412): (alanine--glyoxylate aminotransferase 2) The protein encoded by this gene is a class III pyridoxal-phosphate-dependent mitochondrial aminotransferase. It catalyzes the conversion of glyoxylate to glycine using L-alanine as the amino donor. It is an important regulator of methylarginines and is involved in the control of blood pressure in kidney. Polymorphisms in this gene affect methylarginine and beta-aminoisobutyrate metabolism, and are associated with carotid atherosclerosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=3.32 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGXT2	NM_031900.4	c.354T>C	p.His118=	synonymous_variant	3/14	ENST00000231420.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGXT2	ENST00000231420.11	c.354T>C	p.His118=	synonymous_variant	3/14	1	NM_031900.4	P1
AGXT2	ENST00000510428.1	c.354T>C	p.His118=	synonymous_variant	3/13	1
AGXT2	ENST00000618015.4	c.354T>C	p.His118=	synonymous_variant	3/12	5
AGXT2	ENST00000505542.1	n.263T>C		non_coding_transcript_exon_variant	2/5	2

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78585 AN: 151930 Hom.: 21146 Cov.: 32

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.548

GnomAD3 exomes AF: 0.491 AC: 123150 AN: 250962 Hom.: 32545 AF XY: 0.496 AC XY: 67351 AN XY: 135668

Gnomad AFR exome AF: 0.428

Gnomad AMR exome AF: 0.341

Gnomad ASJ exome AF: 0.549

Gnomad EAS exome AF: 0.239

Gnomad SAS exome AF: 0.386

Gnomad FIN exome AF: 0.547

Gnomad NFE exome AF: 0.597

Gnomad OTH exome AF: 0.530

GnomAD4 exome AF: 0.560 AC: 818158 AN: 1460910 Hom.: 235492 Cov.: 47 AF XY: 0.556 AC XY: 404429 AN XY: 726828

Gnomad4 AFR exome AF: 0.425

Gnomad4 AMR exome AF: 0.355

Gnomad4 ASJ exome AF: 0.548

Gnomad4 EAS exome AF: 0.244

Gnomad4 SAS exome AF: 0.389

Gnomad4 FIN exome AF: 0.555

Gnomad4 NFE exome AF: 0.599

Gnomad4 OTH exome AF: 0.541

GnomAD4 genome AF: 0.517 AC: 78611 AN: 152048 Hom.: 21152 Cov.: 32 AF XY: 0.512 AC XY: 38038 AN XY: 74304

Gnomad4 AFR AF: 0.434

Gnomad4 AMR AF: 0.471

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.546

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.545

Alfa AF: 0.571 Hom.: 21170

Bravo AF: 0.507

Asia WGS AF: 0.332 AC: 1153 AN: 3478

EpiCase AF: 0.608

EpiControl AF: 0.601

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	9.0
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs2279651; hg19: chr5-35039437; COSMIC: COSV51484472;