5-35010047-C-T
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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
NM_031900.4 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 5.68
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 |
---|---|---|---|---|---|---|---|
AGXT2 | NM_031900.4 | c.1291G>A | p.Val431Ile | missense_variant | 12/14 | ENST00000231420.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGXT2 | ENST00000231420.11 | c.1291G>A | p.Val431Ile | missense_variant | 12/14 | 1 | NM_031900.4 | P1 | |
AGXT2 | ENST00000510428.1 | c.1066G>A | p.Val356Ile | missense_variant | 10/13 | 1 | |||
AGXT2 | ENST00000618015.4 | c.1066G>A | p.Val356Ile | missense_variant | 10/12 | 5 | |||
AGXT2 | ENST00000512135.5 | n.961G>A | non_coding_transcript_exon_variant | 4/6 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000296 AC: 45AN: 152202Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000215 AC: 54AN: 251382Hom.: 0 AF XY: 0.000177 AC XY: 24AN XY: 135856
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GnomAD4 exome AF: 0.000389 AC: 569AN: 1461880Hom.: 0 Cov.: 35 AF XY: 0.000366 AC XY: 266AN XY: 727242
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GnomAD4 genome AF: 0.000296 AC: 45AN: 152202Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14AN XY: 74356
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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 | May 07, 2024 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;.
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Benign
N;.;N
REVEL
Uncertain
Sift
Benign
D;.;D
Sift4G
Benign
T;D;D
Polyphen
D;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at