5-34998760-G-C

Variant names:

• chr5-34998760-G-C
• rs200627716
• NM_031900.4:c.1504C>G

Variant summary

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

The NM_031900.4(AGXT2):​c.1504C>G​(p.Arg502Gly) 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AGXT2 NM_031900.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.12

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=0.38536718).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGXT2	NM_031900.4	c.1504C>G	p.Arg502Gly	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.1504C>G	p.Arg502Gly	missense_variant	Exon 14 of 14	1	NM_031900.4	ENSP00000231420.6
AGXT2	ENST00000510428.1	c.1279C>G	p.Arg427Gly	missense_variant	Exon 12 of 13	1		ENSP00000422799.1
AGXT2	ENST00000618015.4	c.1279C>G	p.Arg427Gly	missense_variant	Exon 12 of 12	5		ENSP00000479154.1
AGXT2	ENST00000512135.5	n.1174C>G		non_coding_transcript_exon_variant	Exon 6 of 6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.37	T;.;.
Eigen	Benign	-0.035
Eigen_PC	Benign	0.049
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.80	T;T;.
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;.;.
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-3.5	D;.;D
REVEL	Benign	0.13
Sift	Benign	0.14	T;.;D
Sift4G	Benign	0.21	T;T;T
Polyphen		0.22	B;.;.
Vest4		0.34
MutPred		0.53		Loss of MoRF binding (P = 0.0143);.;.;
MVP		0.68
MPC		0.094
ClinPred		0.64	D
GERP RS		5.7
Varity_R		0.44
gMVP		0.46

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

Other links and lift over

dbSNP: rs200627716; hg19: chr5-34998865;