5-35010047-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_031900.4(AGXT2):​c.1291G>A​(p.Val431Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00038 in 1,614,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00039 ( 0 hom. )

Consequence

AGXT2
NM_031900.4 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.68
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3231038).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AGXT2NM_031900.4 linkuse as main transcriptc.1291G>A p.Val431Ile missense_variant 12/14 ENST00000231420.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AGXT2ENST00000231420.11 linkuse as main transcriptc.1291G>A p.Val431Ile missense_variant 12/141 NM_031900.4 P1Q9BYV1-1
AGXT2ENST00000510428.1 linkuse as main transcriptc.1066G>A p.Val356Ile missense_variant 10/131 Q9BYV1-2
AGXT2ENST00000618015.4 linkuse as main transcriptc.1066G>A p.Val356Ile missense_variant 10/125 Q9BYV1-2
AGXT2ENST00000512135.5 linkuse as main transcriptn.961G>A non_coding_transcript_exon_variant 4/62

Frequencies

GnomAD3 genomes
AF:
0.000296
AC:
45
AN:
152202
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000169
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:
0.000559
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000215
AC:
54
AN:
251382
Hom.:
0
AF XY:
0.000177
AC XY:
24
AN XY:
135856
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000431
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000389
AC:
569
AN:
1461880
Hom.:
0
Cov.:
35
AF XY:
0.000366
AC XY:
266
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000499
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
AF:
0.000296
AC:
45
AN:
152202
Hom.:
0
Cov.:
33
AF XY:
0.000188
AC XY:
14
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.000169
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000559
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000413
Hom.:
0
Bravo
AF:
0.000298
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.00104
AC:
4
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00128
AC:
11
ExAC
AF:
0.000222
AC:
27
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000382
EpiControl
AF:
0.000593

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 submitterclinical testingAmbry GeneticsMay 07, 2024The c.1291G>A (p.V431I) alteration is located in exon 12 (coding exon 12) of the AGXT2 gene. This alteration results from a G to A substitution at nucleotide position 1291, causing the valine (V) at amino acid position 431 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
0.089
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.19
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
T;.;.
Eigen
Benign
-0.025
Eigen_PC
Benign
-0.013
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.83
T;T;.
M_CAP
Benign
0.052
D
MetaRNN
Benign
0.32
T;T;T
MetaSVM
Uncertain
0.44
D
MutationAssessor
Benign
1.2
L;.;.
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-0.98
N;.;N
REVEL
Uncertain
0.41
Sift
Benign
0.033
D;.;D
Sift4G
Benign
0.065
T;D;D
Polyphen
1.0
D;.;.
Vest4
0.33
MVP
0.71
MPC
0.17
ClinPred
0.12
T
GERP RS
3.9
Varity_R
0.21
gMVP
0.75

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.

Other links and lift over

dbSNP: rs142368612; hg19: chr5-35010152; API