rs466067

Positions:

• chr5-35010033-A-G
• chr5-35010033-A-T

Variant summary

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

The NM_031900.4(AGXT2):​c.1305T>C​(p.Gly435=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.981 in 1,614,192 control chromosomes in the GnomAD database, including 778,423 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 0.95 (69204 hom., cov: 33)
  • Exomes 𝑓: 0.98 (709219 hom.)
• Consequence: AGXT2 NM_031900.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.406

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=-0.6).
• BP7: Synonymous conserved (PhyloP=0.406 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGXT2	NM_031900.4	c.1305T>C	p.Gly435=	synonymous_variant	12/14	ENST00000231420.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGXT2	ENST00000231420.11	c.1305T>C	p.Gly435=	synonymous_variant	12/14	1	NM_031900.4	P1
AGXT2	ENST00000510428.1	c.1080T>C	p.Gly360=	synonymous_variant	10/13	1
AGXT2	ENST00000618015.4	c.1080T>C	p.Gly360=	synonymous_variant	10/12	5
AGXT2	ENST00000512135.5	n.975T>C		non_coding_transcript_exon_variant	4/6	2

Frequencies

GnomAD3 genomes AF: 0.951 AC: 144775 AN: 152186 Hom.: 69155 Cov.: 33

Gnomad AFR AF: 0.875

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.964

Gnomad ASJ AF: 0.994

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.903

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.959

GnomAD3 exomes AF: 0.960 AC: 241374 AN: 251420 Hom.: 116369 AF XY: 0.961 AC XY: 130651 AN XY: 135888

Gnomad AFR exome AF: 0.870

Gnomad AMR exome AF: 0.961

Gnomad ASJ exome AF: 0.995

Gnomad EAS exome AF: 0.804

Gnomad SAS exome AF: 0.911

Gnomad FIN exome AF: 0.999

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.981

GnomAD4 exome AF: 0.984 AC: 1438664 AN: 1461888 Hom.: 709219 Cov.: 65 AF XY: 0.983 AC XY: 714539 AN XY: 727248

Gnomad4 AFR exome AF: 0.870

Gnomad4 AMR exome AF: 0.960

Gnomad4 ASJ exome AF: 0.995

Gnomad4 EAS exome AF: 0.822

Gnomad4 SAS exome AF: 0.911

Gnomad4 FIN exome AF: 0.999

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.972

GnomAD4 genome AF: 0.951 AC: 144878 AN: 152304 Hom.: 69204 Cov.: 33 AF XY: 0.950 AC XY: 70738 AN XY: 74480

Gnomad4 AFR AF: 0.875

Gnomad4 AMR AF: 0.964

Gnomad4 ASJ AF: 0.994

Gnomad4 EAS AF: 0.800

Gnomad4 SAS AF: 0.903

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.960

Alfa AF: 0.987 Hom.: 86711

Bravo AF: 0.946

Asia WGS AF: 0.857 AC: 2982 AN: 3478

EpiCase AF: 0.999

EpiControl AF: 0.999

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	6.6
DANN	Benign	0.74

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: rs466067; hg19: chr5-35010138; COSMIC: COSV51486688; COSMIC: COSV51486688;