5-35039381-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031900.4(AGXT2):c.305G>A(p.Ser102Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 1,613,970 control chromosomes in the GnomAD database, including 630,929 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S102I) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.89 (61477 hom., cov: 32)
  • Exomes 𝑓: 0.88 (569452 hom.)
• Consequence: AGXT2 NM_031900.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.6253797E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGXT2	NM_031900.4	c.305G>A	p.Ser102Asn	missense_variant	3/14	ENST00000231420.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGXT2	ENST00000231420.11	c.305G>A	p.Ser102Asn	missense_variant	3/14	1	NM_031900.4	P1
AGXT2	ENST00000510428.1	c.305G>A	p.Ser102Asn	missense_variant	3/13	1
AGXT2	ENST00000618015.4	c.305G>A	p.Ser102Asn	missense_variant	3/12	5
AGXT2	ENST00000505542.1	n.214G>A		non_coding_transcript_exon_variant	2/5	2

Frequencies

GnomAD3 genomes AF: 0.893 AC: 135945 AN: 152152 Hom.: 61418 Cov.: 32

Gnomad AFR AF: 0.973

Gnomad AMI AF: 0.919

Gnomad AMR AF: 0.779

Gnomad ASJ AF: 0.879

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.832

Gnomad FIN AF: 0.900

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.900

Gnomad OTH AF: 0.902

GnomAD3 exomes AF: 0.831 AC: 208811 AN: 251204 Hom.: 89180 AF XY: 0.840 AC XY: 114008 AN XY: 135752

Gnomad AFR exome AF: 0.975

Gnomad AMR exome AF: 0.624

Gnomad ASJ exome AF: 0.882

Gnomad EAS exome AF: 0.525

Gnomad SAS exome AF: 0.839

Gnomad FIN exome AF: 0.896

Gnomad NFE exome AF: 0.903

Gnomad OTH exome AF: 0.853

GnomAD4 exome AF: 0.879 AC: 1285030 AN: 1461700 Hom.: 569452 Cov.: 65 AF XY: 0.879 AC XY: 639214 AN XY: 727168

Gnomad4 AFR exome AF: 0.978

Gnomad4 AMR exome AF: 0.645

Gnomad4 ASJ exome AF: 0.878

Gnomad4 EAS exome AF: 0.544

Gnomad4 SAS exome AF: 0.837

Gnomad4 FIN exome AF: 0.898

Gnomad4 NFE exome AF: 0.900

Gnomad4 OTH exome AF: 0.873

GnomAD4 genome AF: 0.894 AC: 136056 AN: 152270 Hom.: 61477 Cov.: 32 AF XY: 0.889 AC XY: 66197 AN XY: 74452

Gnomad4 AFR AF: 0.973

Gnomad4 AMR AF: 0.778

Gnomad4 ASJ AF: 0.879

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.833

Gnomad4 FIN AF: 0.900

Gnomad4 NFE AF: 0.900

Gnomad4 OTH AF: 0.898

Alfa AF: 0.892 Hom.: 125160

Bravo AF: 0.883

TwinsUK AF: 0.907 AC: 3365

ALSPAC AF: 0.897 AC: 3457

ESP6500AA AF: 0.970 AC: 4274

ESP6500EA AF: 0.906 AC: 7793

ExAC AF: 0.844 AC: 102424

Asia WGS AF: 0.724 AC: 2514 AN: 3478

EpiCase AF: 0.905

EpiControl AF: 0.905

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.77
Cadd	Benign	15
Dann	Benign	0.97
DEOGEN2	Benign	0.095	T;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.38	T;T;.
MetaRNN	Benign	0.0000016	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-2.1	N;N;N
MutationTaster	Benign	1.0	P
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.90	N;.;N
REVEL	Benign	0.13
Sift	Benign	0.33	T;.;T
Sift4G	Benign	0.37	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.030
MPC		0.069
ClinPred		0.011	T
GERP RS		3.3
Varity_R		0.059
gMVP		0.17

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: rs37370; hg19: chr5-35039486; COSMIC: COSV51492175;