rs4344931

Positions:

• chr2-240879110-A-C
• chr2-240879110-A-G
• chr2-240879110-A-T

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.*289A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 532,554 control chromosomes in the GnomAD database, including 130,757 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (40986 hom., cov: 32)
  • Exomes 𝑓: 0.68 (89771 hom.)
• Consequence: AGXT NM_000030.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:3
• Conservation: PhyloP100: -3.97

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-240879110-A-C is Benign according to our data. Variant chr2-240879110-A-C is described in ClinVar as [Benign]. Clinvar id is 204064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGXT	NM_000030.3	c.*289A>C		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.*289A>C		3_prime_UTR_variant	11/11	1	NM_000030.3	ENSP00000302620.3
AGXT	ENST00000470255.1	n.1246A>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110609 AN: 151960 Hom.: 40945 Cov.: 32

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.696

GnomAD4 exome AF: 0.683 AC: 259740 AN: 380478 Hom.: 89771 Cov.: 0 AF XY: 0.673 AC XY: 134824 AN XY: 200188

Gnomad4 AFR exome AF: 0.849

Gnomad4 AMR exome AF: 0.558

Gnomad4 ASJ exome AF: 0.606

Gnomad4 EAS exome AF: 0.723

Gnomad4 SAS exome AF: 0.544

Gnomad4 FIN exome AF: 0.738

Gnomad4 NFE exome AF: 0.705

Gnomad4 OTH exome AF: 0.690

GnomAD4 genome AF: 0.728 AC: 110697 AN: 152076 Hom.: 40986 Cov.: 32 AF XY: 0.723 AC XY: 53712 AN XY: 74332

Gnomad4 AFR AF: 0.852

Gnomad4 AMR AF: 0.592

Gnomad4 ASJ AF: 0.593

Gnomad4 EAS AF: 0.736

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.745

Gnomad4 NFE AF: 0.702

Gnomad4 OTH AF: 0.690

Alfa AF: 0.692 Hom.: 36374

Bravo AF: 0.724

Asia WGS AF: 0.653 AC: 2276 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

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	-0.91
CADD	Benign	0.16
DANN	Benign	0.47

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: rs4344931; hg19: chr2-241818527;