5-35010033-A-T

Position:

• chr5-35010033-A-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_031900.4(AGXT2):​c.1305T>A​(p.Gly435Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• 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]

AGXT2 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=0.406 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGXT2	NM_031900.4	c.1305T>A	p.Gly435Gly	synonymous_variant	12/14	ENST00000231420.11	NP_114106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGXT2	ENST00000231420.11	c.1305T>A	p.Gly435Gly	synonymous_variant	12/14	1	NM_031900.4	ENSP00000231420.6
AGXT2	ENST00000510428.1	c.1080T>A	p.Gly360Gly	synonymous_variant	10/13	1		ENSP00000422799.1
AGXT2	ENST00000618015.4	c.1080T>A	p.Gly360Gly	synonymous_variant	10/12	5		ENSP00000479154.1
AGXT2	ENST00000512135.5	n.975T>A		non_coding_transcript_exon_variant	4/6	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 65

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	6.3
DANN	Benign	0.68

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;