rs40200

Variant names:

• chr5-35045640-A-G
• rs40200
• NM_031900.4:c.88+2165T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031900.4(AGXT2):​c.88+2165T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 152,034 control chromosomes in the GnomAD database, including 54,671 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.84 (54671 hom., cov: 31)
• Consequence: AGXT2 NM_031900.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.609
• Publications: 16 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGXT2	NM_031900.4	c.88+2165T>C		intron_variant	Intron 1 of 13	ENST00000231420.11	NP_114106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGXT2	ENST00000231420.11	c.88+2165T>C		intron_variant	Intron 1 of 13	1	NM_031900.4	ENSP00000231420.6
AGXT2	ENST00000510428.1	c.88+2165T>C		intron_variant	Intron 1 of 12	1		ENSP00000422799.1
AGXT2	ENST00000618015.4	c.88+2165T>C		intron_variant	Intron 1 of 11	5		ENSP00000479154.1
AGXT2	ENST00000505542.1	n.86+2165T>C		intron_variant	Intron 1 of 4	2

Frequencies

GnomAD3 genomes AF: 0.844 AC: 128166 AN: 151918 Hom.: 54643 Cov.: 31

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.919

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.874

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.900

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.900

Gnomad OTH AF: 0.869

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.844 AC: 128241 AN: 152034 Hom.: 54671 Cov.: 31 AF XY: 0.841 AC XY: 62460 AN XY: 74310

African (AFR) AF: 0.797 AC: 33020 AN: 41428

American (AMR) AF: 0.766 AC: 11697 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.874 AC: 3034 AN: 3472

East Asian (EAS) AF: 0.549 AC: 2830 AN: 5158

South Asian (SAS) AF: 0.832 AC: 4007 AN: 4814

European-Finnish (FIN) AF: 0.900 AC: 9512 AN: 10566

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.900 AC: 61208 AN: 68000

Other (OTH) AF: 0.866 AC: 1827 AN: 2110

Alfa AF: 0.876 Hom.: 267499

Bravo AF: 0.826

Asia WGS AF: 0.706 AC: 2454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	6.3
DANN	Benign	0.77
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs40200; hg19: chr5-35045745;