dbSNP rs180749: AGXT2:p.Thr212Ile (chr5-35033500-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

Publications

34 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AGXT2	NM_031900.4 link	c.635C>T	p.Thr212Ile	missense_variant	Exon 6 of 14	ENST00000231420.11	NP_114106.1	Q9BYV1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AGXT2	ENST00000231420.11 link	c.635C>T	p.Thr212Ile	missense_variant	Exon 6 of 14	1	NM_031900.4	ENSP00000231420.6	Q9BYV1-1
AGXT2	ENST00000510428.1 link	c.635C>T	p.Thr212Ile	missense_variant	Exon 6 of 13	1		ENSP00000422799.1	Q9BYV1-2
AGXT2	ENST00000618015.4 link	c.635C>T	p.Thr212Ile	missense_variant	Exon 6 of 12	5		ENSP00000479154.1	Q9BYV1-2
AGXT2	ENST00000505542.1 link	n.544C>T		non_coding_transcript_exon_variant	Exon 5 of 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

GnomAD2 exomes

AF:

0.951

AC:

238991

AN:

251314

AF XY:

0.954

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 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

African (AFR)

AF:

0.825

AC:

27610

AN:

33456

American (AMR)

AF:

0.936

AC:

41840

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.995

AC:

25990

AN:

26130

East Asian (EAS)

AF:

0.794

AC:

31498

AN:

39682

South Asian (SAS)

AF:

0.909

AC:

78381

AN:

86248

European-Finnish (FIN)

AF:

0.996

AC:

53207

AN:

53416

Middle Eastern (MID)

AF:

0.989

AC:

5706

AN:

5768

European-Non Finnish (NFE)

AF:

0.999

AC:

1110672

AN:

1111740

Other (OTH)

AF:

0.965

AC:

58280

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

1422

2843

4265

5686

7108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21634

43268

64902

86536

108170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.936

AC:

142526

AN:

152210

Hom.:

67233

Cov.:

AF XY:

0.935

AC XY:

69586

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.830

AC:

34441

AN:

41504

American (AMR)

AF:

0.952

AC:

14563

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.994

AC:

3452

AN:

3472

East Asian (EAS)

AF:

0.777

AC:

4004

AN:

5150

South Asian (SAS)

AF:

0.901

AC:

4339

AN:

4814

European-Finnish (FIN)

AF:

0.998

AC:

10593

AN:

10616

Middle Eastern (MID)

AF:

0.986

AC:

290

AN:

294

European-Non Finnish (NFE)

AF:

0.998

AC:

67929

AN:

68038

Other (OTH)

AF:

0.948

AC:

2003

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

413

826

1240

1653

2066

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

906

1812

2718

3624

4530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.972

Hom.:

240480

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

(source)

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

PhyloP100

-0.91

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over