rs187490

Positions:

• chr5-35045022-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000231420.11(AGXT2):​c.88+2783T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,068 control chromosomes in the GnomAD database, including 9,386 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 0.34 (9386 hom., cov: 32)
• Consequence: AGXT2 ENST00000231420.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.443

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGXT2	NM_031900.4	c.88+2783T>C		intron_variant		ENST00000231420.11	NP_114106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGXT2	ENST00000231420.11	c.88+2783T>C		intron_variant		1	NM_031900.4	ENSP00000231420	P1
AGXT2	ENST00000510428.1	c.88+2783T>C		intron_variant		1		ENSP00000422799
AGXT2	ENST00000618015.4	c.88+2783T>C		intron_variant		5		ENSP00000479154
AGXT2	ENST00000505542.1	n.86+2783T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52365 AN: 151948 Hom.: 9376 Cov.: 32

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.335

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.345 AC: 52410 AN: 152068 Hom.: 9386 Cov.: 32 AF XY: 0.346 AC XY: 25737 AN XY: 74320

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.445

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.335

Alfa AF: 0.319 Hom.: 2596

Bravo AF: 0.340

Asia WGS AF: 0.378 AC: 1315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.44

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: rs187490; hg19: chr5-35045127;