rs12695032

Positions:

• chr2-240876056-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000030.3(AGXT):​c.846+52G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 1,593,468 control chromosomes in the GnomAD database, including 229,072 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (16303 hom., cov: 34)
  • Exomes 𝑓: 0.53 (212769 hom.)
• Consequence: AGXT NM_000030.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:3
• Conservation: PhyloP100: -1.96

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-240876056-G-A is Benign according to our data. Variant chr2-240876056-G-A is described in ClinVar as [Benign]. Clinvar id is 204054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGXT	NM_000030.3	c.846+52G>A		intron_variant		ENST00000307503.4	NP_000021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGXT	ENST00000307503.4	c.846+52G>A		intron_variant		1	NM_000030.3	ENSP00000302620.3
AGXT	ENST00000476698.1	n.*43G>A		downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65518 AN: 151994 Hom.: 16307 Cov.: 34

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.447

GnomAD3 exomes AF: 0.474 AC: 113347 AN: 239088 Hom.: 28785 AF XY: 0.482 AC XY: 62281 AN XY: 129316

Gnomad AFR exome AF: 0.192

Gnomad AMR exome AF: 0.340

Gnomad ASJ exome AF: 0.428

Gnomad EAS exome AF: 0.334

Gnomad SAS exome AF: 0.388

Gnomad FIN exome AF: 0.636

Gnomad NFE exome AF: 0.573

Gnomad OTH exome AF: 0.506

GnomAD4 exome AF: 0.535 AC: 770956 AN: 1441356 Hom.: 212769 Cov.: 31 AF XY: 0.532 AC XY: 381519 AN XY: 717402

Gnomad4 AFR exome AF: 0.186

Gnomad4 AMR exome AF: 0.349

Gnomad4 ASJ exome AF: 0.425

Gnomad4 EAS exome AF: 0.312

Gnomad4 SAS exome AF: 0.389

Gnomad4 FIN exome AF: 0.632

Gnomad4 NFE exome AF: 0.572

Gnomad4 OTH exome AF: 0.497

GnomAD4 genome AF: 0.431 AC: 65516 AN: 152112 Hom.: 16303 Cov.: 34 AF XY: 0.429 AC XY: 31934 AN XY: 74358

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.647

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.445

Alfa AF: 0.513 Hom.: 8267

Bravo AF: 0.405

Asia WGS AF: 0.346 AC: 1206 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1 Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary hyperoxaluria, type I Uncertain:1 Benign:1

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Uncertain significance, no assertion criteria provided	research	Clinical Biochemistry Laboratory, Health Services Laboratory	Nov 27, 2014	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 07, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.11
DANN	Benign	0.58

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: rs12695032; hg19: chr2-241815473;