chr5-35003007-G-A

Variant names:

• chr5-35003007-G-A
• rs468327
• NM_031900.4:c.1437+756C>T

Variant summary

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

The NM_031900.4(AGXT2):​c.1437+756C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,018 control chromosomes in the GnomAD database, including 5,761 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 0.27 (5761 hom., cov: 32)
• Consequence: AGXT2 NM_031900.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163
• Publications: 12 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGXT2	NM_031900.4	c.1437+756C>T		intron_variant	Intron 13 of 13	ENST00000231420.11	NP_114106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGXT2	ENST00000231420.11	c.1437+756C>T		intron_variant	Intron 13 of 13	1	NM_031900.4	ENSP00000231420.6
AGXT2	ENST00000510428.1	c.1212+756C>T		intron_variant	Intron 11 of 12	1		ENSP00000422799.1
AGXT2	ENST00000618015.4	c.1212+756C>T		intron_variant	Intron 11 of 11	5		ENSP00000479154.1
AGXT2	ENST00000512135.5	n.1107+756C>T		intron_variant	Intron 5 of 5	2

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40599 AN: 151900 Hom.: 5741 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.267 AC: 40663 AN: 152018 Hom.: 5761 Cov.: 32 AF XY: 0.268 AC XY: 19919 AN XY: 74262

African (AFR) AF: 0.327 AC: 13550 AN: 41448

American (AMR) AF: 0.315 AC: 4822 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 674 AN: 3472

East Asian (EAS) AF: 0.474 AC: 2439 AN: 5150

South Asian (SAS) AF: 0.234 AC: 1129 AN: 4816

European-Finnish (FIN) AF: 0.212 AC: 2242 AN: 10568

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14955 AN: 67960

Other (OTH) AF: 0.257 AC: 543 AN: 2110

Alfa AF: 0.243 Hom.: 10630

Bravo AF: 0.284

Asia WGS AF: 0.364 AC: 1266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.44
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

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: rs468327; hg19: chr5-35003112;