rs180177290

chr2-240877555-C-Achr2-240877555-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_000030.3(AGXT):c.865C>A(p.Arg289Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,397,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R289H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: AGXT NM_000030.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a hotspot region, there are 5 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 4 uncertain in NM_000030.3
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21810529).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGXT	NM_000030.3	c.865C>A	p.Arg289Ser	missense_variant	9/11	ENST00000307503.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGXT	ENST00000307503.4	c.865C>A	p.Arg289Ser	missense_variant	9/11	1	NM_000030.3	P1
AGXT	ENST00000470255.1	n.643C>A		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1397394 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 689126

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
Cadd	Benign	17
Dann	Benign	0.96
DEOGEN2	Uncertain	0.48	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.15	N
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.22	T
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	0.99	D
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.56
Sift	Benign	0.28	T
Sift4G	Benign	0.72	T
Polyphen		0.0030	B
Vest4		0.099
MutPred		0.61		Loss of catalytic residue at R289 (P = 9e-04);
MVP		0.89
MPC		0.036
ClinPred		0.46	T
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.45
gMVP		0.81

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-241816972;