Variant rs180749 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.635C>T(p.Thr212Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.976 in 1,613,754 control chromosomes in the GnomAD database, including 771,744 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.94 ( 67233 hom., cov: 31)

Exomes 𝑓: 0.98 ( 704511 hom. )

Consequence

AGXT2
NM_031900.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.914

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:

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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=8.9576423E-7).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGXT2	NM_031900.4 linkuse as main transcript	c.635C>T	p.Thr212Ile	missense_variant	6/14	ENST00000231420.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGXT2	ENST00000231420.11 linkuse as main transcript	c.635C>T	p.Thr212Ile	missense_variant	6/14	1	NM_031900.4	P1	Q9BYV1-1
AGXT2	ENST00000510428.1 linkuse as main transcript	c.635C>T	p.Thr212Ile	missense_variant	6/13	1			Q9BYV1-2
AGXT2	ENST00000618015.4 linkuse as main transcript	c.635C>T	p.Thr212Ile	missense_variant	6/12	5			Q9BYV1-2
AGXT2	ENST00000505542.1 linkuse as main transcript	n.544C>T		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

AF:

0.937

AC:

142474

AN:

152092

Hom.:

67217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.831

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.952

Gnomad ASJ

AF:

0.994

Gnomad EAS

AF:

0.778

Gnomad SAS

AF:

0.901

Gnomad FIN

AF:

0.998

Gnomad MID

AF:

0.987

Gnomad NFE

AF:

0.998

Gnomad OTH

AF:

0.948

GnomAD3 exomes

AF:

0.951

AC:

238991

AN:

251314

Hom.:

114306

AF XY:

0.954

AC XY:

129556

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.823

Gnomad AMR exome

AF:

0.934

Gnomad ASJ exome

AF:

0.995

Gnomad EAS exome

AF:

0.788

Gnomad SAS exome

AF:

0.909

Gnomad FIN exome

AF:

0.996

Gnomad NFE exome

AF:

0.998

Gnomad OTH exome

AF:

0.975

GnomAD4 exome

AF:

0.981

AC:

1433184

AN:

1461544

Hom.:

704511

Cov.:

AF XY:

0.979

AC XY:

711996

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.825

Gnomad4 AMR exome

AF:

0.936

Gnomad4 ASJ exome

AF:

0.995

Gnomad4 EAS exome

AF:

0.794

Gnomad4 SAS exome

AF:

0.909

Gnomad4 FIN exome

AF:

0.996

Gnomad4 NFE exome

AF:

0.999

Gnomad4 OTH exome

AF:

0.965

GnomAD4 genome

AF:

0.936

AC:

142526

AN:

152210

Hom.:

67233

Cov.:

AF XY:

0.935

AC XY:

69586

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.830

Gnomad4 AMR

AF:

0.952

Gnomad4 ASJ

AF:

0.994

Gnomad4 EAS

AF:

0.777

Gnomad4 SAS

AF:

0.901

Gnomad4 FIN

AF:

0.998

Gnomad4 NFE

AF:

0.998

Gnomad4 OTH

AF:

0.948

Alfa

AF:

0.982

Hom.:

154774

Bravo

AF:

0.930

TwinsUK

AF:

1.00

AC:

3708

ALSPAC

AF:

0.999

AC:

3849

ESP6500AA

AF:

0.832

AC:

3664

ESP6500EA

AF:

0.999

AC:

8589

ExAC

AF:

0.949

AC:

115226

Asia WGS

AF:

0.830

AC:

2887

AN:

3478

EpiCase

AF:

0.999

EpiControl

AF:

0.999

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.47

CADD

Benign

0.096

DANN

Benign

0.80

DEOGEN2

Benign

0.36

T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.031

T;T;.

MetaRNN

Benign

9.0e-7

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.4

L;L;L

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-3.2

D;.;D

REVEL

Benign

0.17

Sift

Benign

0.30

T;.;T

Sift4G

Benign

0.44

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.077

MPC

0.081

ClinPred

0.0067

GERP RS

-5.2

Varity_R

0.073

gMVP

0.48

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over