rs180177201

chr2-240868890-ACC-Achr2-240868890-ACC-ACchr2-240868890-ACC-ACCC

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1 PP5

The NM_000030.3(AGXT):c.32_33del(p.Pro11GlnfsTer156) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. T9T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AGXT NM_000030.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.775

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 Likely_pathogenic. Variant got 9 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 247 pathogenic variants in the truncated region.
• PP5: Variant 2-240868890-ACC-A is Pathogenic according to our data. Variant chr2-240868890-ACC-A is described in ClinVar as [Pathogenic]. Clinvar id is 204173.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGXT	NM_000030.3	c.32_33del	p.Pro11GlnfsTer156	frameshift_variant	1/11	ENST00000307503.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGXT	ENST00000307503.4	c.32_33del	p.Pro11GlnfsTer156	frameshift_variant	1/11	1	NM_000030.3	P1
AGXT	ENST00000472436.1	n.52_53del		non_coding_transcript_exon_variant	1/5	2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Primary hyperoxaluria, type I Pathogenic:1

Pathogenic, no assertion criteria provided

research

Clinical Biochemistry Laboratory, Health Services Laboratory

Nov 27, 2014

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.20		Position offset: 45

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs180177201; hg19: chr2-241808307;