rs37369

chr5-35037010-C-Achr5-35037010-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_031900.4(AGXT2):c.418G>T(p.Val140Phe) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V140I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AGXT2 NM_031900.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34069765).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGXT2	NM_031900.4	c.418G>T	p.Val140Phe	missense_variant	4/14	ENST00000231420.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGXT2	ENST00000231420.11	c.418G>T	p.Val140Phe	missense_variant	4/14	1	NM_031900.4	P1
AGXT2	ENST00000510428.1	c.418G>T	p.Val140Phe	missense_variant	4/13	1
AGXT2	ENST00000618015.4	c.418G>T	p.Val140Phe	missense_variant	4/12	5
AGXT2	ENST00000505542.1	n.327G>T		non_coding_transcript_exon_variant	3/5	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
Cadd	Benign	4.9
Dann	Uncertain	0.99
DEOGEN2	Benign	0.36	T;.;.
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.77	T;T;.
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.34	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.29	N;N;N
MutationTaster	Benign	0.99	P
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.1	D;.;D
REVEL	Benign	0.063
Sift	Uncertain	0.0020	D;.;D
Sift4G	Uncertain	0.032	D;D;D
Polyphen		0.86	P;.;.
Vest4		0.36
MutPred		0.64		Loss of MoRF binding (P = 0.1353);Loss of MoRF binding (P = 0.1353);Loss of MoRF binding (P = 0.1353);
MVP		0.32
MPC		0.26
ClinPred		0.79	D
GERP RS		0.62
Varity_R		0.35
gMVP		0.85

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: chr5-35037115;