rs4273214

Positions:

• chr2-240878862-C-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.*41C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,530,324 control chromosomes in the GnomAD database, including 108,657 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (8132 hom., cov: 33)
  • Exomes 𝑓: 0.38 (100525 hom.)
• Consequence: AGXT NM_000030.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:4
• Conservation: PhyloP100: -2.35

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=-0.87).
• BP6: Variant 2-240878862-C-A is Benign according to our data. Variant chr2-240878862-C-A is described in ClinVar as [Benign]. Clinvar id is 204063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGXT	NM_000030.3	c.*41C>A		3_prime_UTR_variant	11/11	ENST00000307503.4	NP_000021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGXT	ENST00000307503.4	c.*41C>A		3_prime_UTR_variant	11/11	1	NM_000030.3	ENSP00000302620.3
AGXT	ENST00000470255.1	n.998C>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46763 AN: 152020 Hom.: 8136 Cov.: 33

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.303

GnomAD3 exomes AF: 0.332 AC: 52992 AN: 159740 Hom.: 9258 AF XY: 0.338 AC XY: 28880 AN XY: 85366

Gnomad AFR exome AF: 0.151

Gnomad AMR exome AF: 0.242

Gnomad ASJ exome AF: 0.294

Gnomad EAS exome AF: 0.261

Gnomad SAS exome AF: 0.304

Gnomad FIN exome AF: 0.417

Gnomad NFE exome AF: 0.404

Gnomad OTH exome AF: 0.357

GnomAD4 exome AF: 0.377 AC: 520050 AN: 1378184 Hom.: 100525 Cov.: 26 AF XY: 0.377 AC XY: 256909 AN XY: 682282

Gnomad4 AFR exome AF: 0.144

Gnomad4 AMR exome AF: 0.252

Gnomad4 ASJ exome AF: 0.291

Gnomad4 EAS exome AF: 0.240

Gnomad4 SAS exome AF: 0.302

Gnomad4 FIN exome AF: 0.418

Gnomad4 NFE exome AF: 0.401

Gnomad4 OTH exome AF: 0.351

GnomAD4 genome AF: 0.307 AC: 46762 AN: 152140 Hom.: 8132 Cov.: 33 AF XY: 0.306 AC XY: 22731 AN XY: 74366

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.303

Alfa AF: 0.369 Hom.: 9923

Bravo AF: 0.292

Asia WGS AF: 0.284 AC: 991 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1 Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary hyperoxaluria, type I Uncertain:1 Benign:2

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	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.0
DANN	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs4273214; hg19: chr2-241818279; COSMIC: COSV56755073; COSMIC: COSV56755073;