Variant 5-35026456-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_031900.4(AGXT2):c.824C>T(p.Thr275Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000212 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

AGXT2
NM_031900.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.68

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 Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.745

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGXT2	NM_031900.4 linkuse as main transcript	c.824C>T	p.Thr275Ile	missense_variant	8/14	ENST00000231420.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGXT2	ENST00000231420.11 linkuse as main transcript	c.824C>T	p.Thr275Ile	missense_variant	8/14	1	NM_031900.4	P1	Q9BYV1-1
AGXT2	ENST00000510428.1 linkuse as main transcript	c.824C>T	p.Thr275Ile	missense_variant	8/13	1			Q9BYV1-2
AGXT2	ENST00000618015.4 linkuse as main transcript	c.824C>T	p.Thr275Ile	missense_variant	8/12	5			Q9BYV1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251190

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1461838

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000252

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 02, 2023

The c.824C>T (p.T275I) alteration is located in exon 8 (coding exon 8) of the AGXT2 gene. This alteration results from a C to T substitution at nucleotide position 824, causing the threonine (T) at amino acid position 275 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.16

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.13

T;.;.

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.87

D;D;.

M_CAP

Benign

0.043

MetaRNN

Pathogenic

0.74

D;D;D

MetaSVM

Uncertain

0.27

MutationAssessor

Benign

1.7

L;L;L

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.4

N;.;N

REVEL

Uncertain

0.45

Sift

Benign

0.16

T;.;T

Sift4G

Benign

0.34

T;T;T

Polyphen

0.99

D;.;.

Vest4

0.70

MVP

0.93

MPC

0.11

ClinPred

0.73

GERP RS

4.8

Varity_R

0.13

gMVP

0.67

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