rs180177215

Positions:

• chr2-240870698-AGGT-A

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4_Supporting PP5_Moderate

The NM_000030.3(AGXT):​c.416_418delTGG​(p.Val139del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AGXT NM_000030.3 disruptive_inframe_deletion
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 2.21

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 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_000030.3. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 2-240870698-AGGT-A is Pathogenic according to our data. Variant chr2-240870698-AGGT-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 204184.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGXT	NM_000030.3	c.416_418delTGG	p.Val139del	disruptive_inframe_deletion	3/11	ENST00000307503.4	NP_000021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGXT	ENST00000307503.4	c.416_418delTGG	p.Val139del	disruptive_inframe_deletion	3/11	1	NM_000030.3	ENSP00000302620.3
AGXT	ENST00000472436.1	n.436_438delTGG		non_coding_transcript_exon_variant	3/5	2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

See cases Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein

Mar 30, 2020

ACMG classification criteria: PS4, PM2, PM3, PM4, PP5 -

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)		0.0		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: rs180177215; hg19: chr2-241810115;