rs180177181

Positions:

• chr2-240869191-G-A
• chr2-240869191-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000030.3(AGXT):​c.187G>A​(p.Gly63Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AGXT NM_000030.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.18

Genes affected

AGXT (HGNC:341): (alanine--glyoxylate aminotransferase) This gene is expressed only in the liver and the encoded protein is localized mostly in the peroxisomes, where it is involved in glyoxylate detoxification. Mutations in this gene, some of which alter subcellular targetting, have been associated with type I primary hyperoxaluria. [provided by RefSeq, Jul 2008]

AGXT (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.89

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGXT	NM_000030.3	c.187G>A	p.Gly63Ser	missense_variant	2/11	ENST00000307503.4	NP_000021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGXT	ENST00000307503.4	c.187G>A	p.Gly63Ser	missense_variant	2/11	1	NM_000030.3	ENSP00000302620.3
AGXT	ENST00000472436.1	n.207G>A		non_coding_transcript_exon_variant	2/5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.77	D
Eigen	Pathogenic	0.74
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.53	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	0.65	D
MutationAssessor	Uncertain	2.8	M
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Pathogenic	0.74
Sift	Benign	0.063	T
Sift4G	Benign	0.071	T
Polyphen		1.0	D
Vest4		0.82
MutPred		0.49		Loss of ubiquitination at K61 (P = 0.0901);
MVP		0.98
MPC		0.25
ClinPred		1.0	D
GERP RS		4.1
Varity_R		0.94
gMVP		0.89

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

Publications

LitVar

Other links and lift over

dbSNP: rs180177181; hg19: chr2-241808608;