rs529653742

Variant names:

• chr5-34998807-G-A
• rs529653742
• NM_031900.4:c.1457C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_031900.4(AGXT2):​c.1457C>T​(p.Ser486Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000223 in 1,613,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: AGXT2 NM_031900.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.71
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.26019275).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031900.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGXT2	NM_031900.4	MANE Select	c.1457C>T	p.Ser486Leu	missense	Exon 14 of 14	NP_114106.1	Q9BYV1-1
	AGXT2	NM_001438583.1		c.1454C>T	p.Ser485Leu	missense	Exon 14 of 14	NP_001425512.1
	AGXT2	NM_001438584.1		c.1262C>T	p.Ser421Leu	missense	Exon 12 of 12	NP_001425513.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGXT2	ENST00000231420.11	TSL:1 MANE Select	c.1457C>T	p.Ser486Leu	missense	Exon 14 of 14	ENSP00000231420.6	Q9BYV1-1
	AGXT2	ENST00000510428.1	TSL:1	c.1232C>T	p.Ser411Leu	missense	Exon 12 of 13	ENSP00000422799.1	Q9BYV1-2
	AGXT2	ENST00000853198.1		c.1538C>T	p.Ser513Leu	missense	Exon 15 of 15	ENSP00000523257.1

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

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: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251102 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461348 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727018

African (AFR) AF: 0.000149 AC: 5 AN: 33478

American (AMR) AF: 0.0000671 AC: 3 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53082

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111828

Other (OTH) AF: 0.0000497 AC: 3 AN: 60394

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152304 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74474

African (AFR) AF: 0.000385 AC: 16 AN: 41554

American (AMR) AF: 0.000457 AC: 7 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.0000987 Hom.: 0

Bravo AF: 0.000261

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.044
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		5.7
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.22
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.054	B
Vest4		0.34
MVP		0.65
MPC		0.070
ClinPred		0.87	D
GERP RS		5.6
Varity_R		0.33
gMVP		0.87
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs529653742; hg19: chr5-34998912;