5-35010033-A-G

Variant names:

• chr5-35010033-A-G
• rs466067
• NM_031900.4:c.1305T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_031900.4(AGXT2):​c.1305T>C​(p.Gly435Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.981 in 1,614,192 control chromosomes in the GnomAD database, including 778,423 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 0.95 (69204 hom., cov: 33)
  • Exomes 𝑓: 0.98 (709219 hom.)
• Consequence: AGXT2 NM_031900.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.406
• Publications: 14 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=0.406 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGXT2	NM_031900.4	MANE Select	c.1305T>C	p.Gly435Gly	synonymous	Exon 12 of 14	NP_114106.1
	AGXT2	NM_001438583.1		c.1302T>C	p.Gly434Gly	synonymous	Exon 12 of 14	NP_001425512.1
	AGXT2	NM_001438584.1		c.1110T>C	p.Gly370Gly	synonymous	Exon 10 of 12	NP_001425513.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGXT2	ENST00000231420.11	TSL:1 MANE Select	c.1305T>C	p.Gly435Gly	synonymous	Exon 12 of 14	ENSP00000231420.6
	AGXT2	ENST00000510428.1	TSL:1	c.1080T>C	p.Gly360Gly	synonymous	Exon 10 of 13	ENSP00000422799.1
	AGXT2	ENST00000618015.4	TSL:5	c.1080T>C	p.Gly360Gly	synonymous	Exon 10 of 12	ENSP00000479154.1

Frequencies

GnomAD3 genomes AF: 0.951 AC: 144775 AN: 152186 Hom.: 69155 Cov.: 33

Gnomad AFR AF: 0.875

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.964

Gnomad ASJ AF: 0.994

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.903

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.959

GnomAD2 exomes AF: 0.960 AC: 241374 AN: 251420 AF XY: 0.961

Gnomad AFR exome AF: 0.870

Gnomad AMR exome AF: 0.961

Gnomad ASJ exome AF: 0.995

Gnomad EAS exome AF: 0.804

Gnomad FIN exome AF: 0.999

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.981

GnomAD4 exome AF: 0.984 AC: 1438664 AN: 1461888 Hom.: 709219 Cov.: 65 AF XY: 0.983 AC XY: 714539 AN XY: 727248

African (AFR) AF: 0.870 AC: 29117 AN: 33480

American (AMR) AF: 0.960 AC: 42921 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 25999 AN: 26136

East Asian (EAS) AF: 0.822 AC: 32640 AN: 39700

South Asian (SAS) AF: 0.911 AC: 78590 AN: 86258

European-Finnish (FIN) AF: 0.999 AC: 53367 AN: 53418

Middle Eastern (MID) AF: 0.992 AC: 5719 AN: 5768

European-Non Finnish (NFE) AF: 1.00 AC: 1111593 AN: 1112010

Other (OTH) AF: 0.972 AC: 58718 AN: 60394

GnomAD4 genome AF: 0.951 AC: 144878 AN: 152304 Hom.: 69204 Cov.: 33 AF XY: 0.950 AC XY: 70738 AN XY: 74480

African (AFR) AF: 0.875 AC: 36325 AN: 41530

American (AMR) AF: 0.964 AC: 14749 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.994 AC: 3452 AN: 3472

East Asian (EAS) AF: 0.800 AC: 4136 AN: 5168

South Asian (SAS) AF: 0.903 AC: 4359 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10629 AN: 10632

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67997 AN: 68050

Other (OTH) AF: 0.960 AC: 2029 AN: 2114

Alfa AF: 0.984 Hom.: 108201

Bravo AF: 0.946

Asia WGS AF: 0.857 AC: 2982 AN: 3478

EpiCase AF: 0.999

EpiControl AF: 0.999

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	6.6
DANN	Benign	0.74
PhyloP100		0.41
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: rs466067; hg19: chr5-35010138; COSMIC: COSV51486688; COSMIC: COSV51486688;