rs37369

Variant names:

• chr5-35037010-C-T
• rs37369
• NM_031900.4:c.418G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-35037010-C-T
• chr5-35037010-C-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031900.4(AGXT2):​c.418G>A​(p.Val140Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,614,008 control chromosomes in the GnomAD database, including 32,089 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Affects (no stars).

• Frequency:
  • Genomes: 𝑓 0.25 (8230 hom., cov: 33)
  • Exomes 𝑓: 0.13 (23859 hom.)
• Consequence: AGXT2 NM_031900.4 missense
• Clinical Significance: Affects no assertion criteria provided O:1
• Conservation: PhyloP100: 0.313
• Publications: 96 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0213786E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031900.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGXT2	NM_031900.4	MANE Select	c.418G>A	p.Val140Ile	missense	Exon 4 of 14	NP_114106.1	Q9BYV1-1
	AGXT2	NM_001438583.1		c.415G>A	p.Val139Ile	missense	Exon 4 of 14	NP_001425512.1
	AGXT2	NM_001438584.1		c.418G>A	p.Val140Ile	missense	Exon 4 of 12	NP_001425513.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGXT2	ENST00000231420.11	TSL:1 MANE Select	c.418G>A	p.Val140Ile	missense	Exon 4 of 14	ENSP00000231420.6	Q9BYV1-1
	AGXT2	ENST00000510428.1	TSL:1	c.418G>A	p.Val140Ile	missense	Exon 4 of 13	ENSP00000422799.1	Q9BYV1-2
	AGXT2	ENST00000853198.1		c.499G>A	p.Val167Ile	missense	Exon 5 of 15	ENSP00000523257.1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38529 AN: 152064 Hom.: 8208 Cov.: 33

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0846

Gnomad OTH AF: 0.222

GnomAD2 exomes AF: 0.210 AC: 52796 AN: 251192 AF XY: 0.194

Gnomad AFR exome AF: 0.557

Gnomad AMR exome AF: 0.358

Gnomad ASJ exome AF: 0.0995

Gnomad EAS exome AF: 0.578

Gnomad FIN exome AF: 0.103

Gnomad NFE exome AF: 0.0843

Gnomad OTH exome AF: 0.156

GnomAD4 exome AF: 0.130 AC: 190486 AN: 1461826 Hom.: 23859 Cov.: 41 AF XY: 0.130 AC XY: 94892 AN XY: 727224

African (AFR) AF: 0.563 AC: 18850 AN: 33478

American (AMR) AF: 0.346 AC: 15473 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 2669 AN: 26134

East Asian (EAS) AF: 0.617 AC: 24511 AN: 39696

South Asian (SAS) AF: 0.229 AC: 19737 AN: 86254

European-Finnish (FIN) AF: 0.101 AC: 5377 AN: 53414

Middle Eastern (MID) AF: 0.109 AC: 627 AN: 5764

European-Non Finnish (NFE) AF: 0.0840 AC: 93416 AN: 1111972

Other (OTH) AF: 0.163 AC: 9826 AN: 60392

GnomAD4 genome AF: 0.254 AC: 38595 AN: 152182 Hom.: 8230 Cov.: 33 AF XY: 0.255 AC XY: 18975 AN XY: 74402

African (AFR) AF: 0.547 AC: 22681 AN: 41486

American (AMR) AF: 0.257 AC: 3933 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 378 AN: 3470

East Asian (EAS) AF: 0.580 AC: 2993 AN: 5156

South Asian (SAS) AF: 0.243 AC: 1173 AN: 4828

European-Finnish (FIN) AF: 0.104 AC: 1104 AN: 10594

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0846 AC: 5755 AN: 68032

Other (OTH) AF: 0.227 AC: 479 AN: 2110

Alfa AF: 0.147 Hom.: 16569

Bravo AF: 0.281

TwinsUK AF: 0.0831 AC: 308

ALSPAC AF: 0.0898 AC: 346

ESP6500AA AF: 0.539 AC: 2374

ESP6500EA AF: 0.0853 AC: 734

ExAC AF: 0.211 AC: 25570

Asia WGS AF: 0.413 AC: 1438 AN: 3478

EpiCase AF: 0.0802

EpiControl AF: 0.0803

ClinVar

ClinVar submissions

Significance: Affects

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Beta-aminoisobutyric acid, urinary excretion of (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.056
DANN	Benign	0.65
DEOGEN2	Benign	0.074	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.49	T
MetaRNN	Benign	0.00010	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.1	N
PhyloP100		0.31
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.43	N
REVEL	Benign	0.0070
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0030	B
Vest4		0.040
MPC		0.061
ClinPred		0.00030	T
GERP RS		0.62
Varity_R		0.019
gMVP		0.56
Mutation Taster		=99/1	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: rs37369; hg19: chr5-35037115; COSMIC: COSV51484897;