rs2279651

Variant names:

• chr5-35039332-A-G
• rs2279651
• NM_031900.4:c.354T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_031900.4(AGXT2):​c.354T>C​(p.His118His) 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
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AGXT2	NM_031900.4	c.354T>C	p.His118His	synonymous_variant	Exon 3 of 14	ENST00000231420.11	NP_114106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGXT2	ENST00000231420.11	c.354T>C	p.His118His	synonymous_variant	Exon 3 of 14	1	NM_031900.4	ENSP00000231420.6
AGXT2	ENST00000510428.1	c.354T>C	p.His118His	synonymous_variant	Exon 3 of 13	1		ENSP00000422799.1
AGXT2	ENST00000618015.4	c.354T>C	p.His118His	synonymous_variant	Exon 3 of 12	5		ENSP00000479154.1
AGXT2	ENST00000505542.1	n.263T>C		non_coding_transcript_exon_variant	Exon 2 of 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

GnomAD2 exomes AF: 0.491 AC: 123150 AN: 250962 AF XY: 0.496

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 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

African (AFR) AF: 0.425 AC: 14225 AN: 33454

American (AMR) AF: 0.355 AC: 15888 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 14302 AN: 26116

East Asian (EAS) AF: 0.244 AC: 9696 AN: 39698

South Asian (SAS) AF: 0.389 AC: 33568 AN: 86226

European-Finnish (FIN) AF: 0.555 AC: 29641 AN: 53394

Middle Eastern (MID) AF: 0.528 AC: 3042 AN: 5762

European-Non Finnish (NFE) AF: 0.599 AC: 665169 AN: 1111194

Other (OTH) AF: 0.541 AC: 32627 AN: 60356

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

African (AFR) AF: 0.434 AC: 18003 AN: 41468

American (AMR) AF: 0.471 AC: 7206 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1940 AN: 3472

East Asian (EAS) AF: 0.247 AC: 1273 AN: 5162

South Asian (SAS) AF: 0.384 AC: 1850 AN: 4820

European-Finnish (FIN) AF: 0.546 AC: 5760 AN: 10556

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40669 AN: 67964

Other (OTH) AF: 0.545 AC: 1154 AN: 2116

Alfa AF: 0.571 Hom.: 22546

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
PhyloP100		3.3
Mutation Taster		=100/0	polymorphism (auto)

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