NM_031900.4:c.1451C>A

Variant names:

• chr5-34998813-G-T
• NM_031900.4:c.1451C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_031900.4(AGXT2):​c.1451C>A​(p.Ala484Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,730 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A484A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: AGXT2 NM_031900.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGXT2	NM_031900.4	c.1451C>A	p.Ala484Glu	missense_variant	Exon 14 of 14	ENST00000231420.11	NP_114106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGXT2	ENST00000231420.11	c.1451C>A	p.Ala484Glu	missense_variant	Exon 14 of 14	1	NM_031900.4	ENSP00000231420.6
AGXT2	ENST00000510428.1	c.1226C>A	p.Ala409Glu	missense_variant	Exon 12 of 13	1		ENSP00000422799.1
AGXT2	ENST00000618015.4	c.1226C>A	p.Ala409Glu	missense_variant	Exon 12 of 12	5		ENSP00000479154.1
AGXT2	ENST00000512135.5	n.1121C>A		non_coding_transcript_exon_variant	Exon 6 of 6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460730 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726754

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Uncertain	0.094	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.11	T;.;.
Eigen	Benign	-0.091
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.14	N
LIST_S2	Uncertain	0.95	D;D;.
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.44	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;.;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	1.1	N;.;N
REVEL	Benign	0.20
Sift	Benign	0.030	D;.;D
Sift4G	Uncertain	0.027	D;D;D
Polyphen		0.45	B;.;.
Vest4		0.49
MutPred		0.63		Loss of MoRF binding (P = 0.0915);.;.;
MVP		0.54
MPC		0.087
ClinPred		0.83	D
GERP RS		3.6
Varity_R		0.16
gMVP		0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-34998918; COSMIC: COSV99183720;