Genetic Variant AGXT2:p.Thr212Ser (chr5-35033500-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031900.4(AGXT2):c.635C>G(p.Thr212Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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 0.0 ( 0 hom., cov: 31)

Failed GnomAD Quality Control

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.074600995).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AGXT2	NM_031900.4	MANE Select	c.635C>G	p.Thr212Ser	missense	Exon 6 of 14	NP_114106.1
AGXT2	NM_001438583.1		c.632C>G	p.Thr211Ser	missense	Exon 6 of 14	NP_001425512.1
AGXT2	NM_001438584.1		c.635C>G	p.Thr212Ser	missense	Exon 6 of 12	NP_001425513.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AGXT2	ENST00000231420.11	TSL:1 MANE Select	c.635C>G	p.Thr212Ser	missense	Exon 6 of 14	ENSP00000231420.6
AGXT2	ENST00000510428.1	TSL:1	c.635C>G	p.Thr212Ser	missense	Exon 6 of 13	ENSP00000422799.1
AGXT2	ENST00000618015.4	TSL:5	c.635C>G	p.Thr212Ser	missense	Exon 6 of 12	ENSP00000479154.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152112

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74304

African (AFR)

AF:

0.00

AC:

AN:

41398

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68046

Other (OTH)

AF:

0.00

AC:

AN:

2090

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.013

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.11

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.028

M_CAP

Benign

0.048

MetaRNN

Benign

0.075

MetaSVM

Benign

-0.78

MutationAssessor

Benign

0.33

PhyloP100

-0.91

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.39

REVEL

Benign

0.12

Sift

Benign

0.31

Sift4G

Benign

0.52

Polyphen

0.0

Vest4

0.15

MutPred

0.37

Loss of phosphorylation at T212 (P = 0.0651)

MVP

0.38

MPC

0.067

ClinPred

0.21

GERP RS

-5.2

Varity_R

0.032

gMVP

0.41

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over