Variant chr5-35037010-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 14/20 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

Scores

Clinical Significance

Affects no assertion criteria provided O:1

Conservation

PhyloP100: 0.313

Variant links:

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 links:

AGXT2 (HGNC:):

AGXT2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGXT2	NM_031900.4 linkuse as main transcript	c.418G>A	p.Val140Ile	missense_variant	4/14	ENST00000231420.11	NP_114106.1	Q9BYV1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AGXT2	ENST00000231420.11 linkuse as main transcript	c.418G>A	p.Val140Ile	missense_variant	4/14	1	NM_031900.4	ENSP00000231420.6	Q9BYV1-1
AGXT2	ENST00000510428.1 linkuse as main transcript	c.418G>A	p.Val140Ile	missense_variant	4/13	1		ENSP00000422799.1	Q9BYV1-2
AGXT2	ENST00000618015.4 linkuse as main transcript	c.418G>A	p.Val140Ile	missense_variant	4/12	5		ENSP00000479154.1	Q9BYV1-2
AGXT2	ENST00000505542.1 linkuse as main transcript	n.327G>A		non_coding_transcript_exon_variant	3/5	2

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38529

AN:

152064

Hom.:

8208

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.210

AC:

52796

AN:

251192

Hom.:

9552

AF XY:

0.194

AC XY:

26272

AN XY:

135752

show subpopulations

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 SAS exome

AF:

0.227

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.:

AF XY:

0.130

AC XY:

94892

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.563

Gnomad4 AMR exome

AF:

0.346

Gnomad4 ASJ exome

AF:

0.102

Gnomad4 EAS exome

AF:

0.617

Gnomad4 SAS exome

AF:

0.229

Gnomad4 FIN exome

AF:

0.101

Gnomad4 NFE exome

AF:

0.0840

Gnomad4 OTH exome

AF:

0.163

GnomAD4 genome

AF:

0.254

AC:

38595

AN:

152182

Hom.:

8230

Cov.:

AF XY:

0.255

AC XY:

18975

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.547

Gnomad4 AMR

AF:

0.257

Gnomad4 ASJ

AF:

0.109

Gnomad4 EAS

AF:

0.580

Gnomad4 SAS

AF:

0.243

Gnomad4 FIN

AF:

0.104

Gnomad4 NFE

AF:

0.0846

Gnomad4 OTH

AF:

0.227

Alfa

AF:

0.127

Hom.:

6464

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

Significance: Affects

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Beta-aminoisobutyric acid, urinary excretion of

Other:1

Affects, no assertion criteria provided

literature only

OMIM

Jun 01, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.75

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

LIST_S2

Benign

0.49

T;T;.

MetaRNN

Benign

0.00010

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.1

N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

0.43

N;.;N

REVEL

Benign

0.0070

Sift

Benign

1.0

T;.;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0030

B;.;.

Vest4

0.040

MPC

0.061

ClinPred

0.00030

GERP RS

0.62

Varity_R

0.019

gMVP

0.56

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over