2-240875891-A-G

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.777-44A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 1,599,832 control chromosomes in the GnomAD database, including 438,654 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (47651 hom., cov: 34)
  • Exomes 𝑓: 0.73 (391003 hom.)
• Consequence: AGXT NM_000030.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:2
• Conservation: PhyloP100: -5.24

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=-0.94).
• BP6: Variant 2-240875891-A-G is Benign according to our data. Variant chr2-240875891-A-G is described in ClinVar as [Benign]. Clinvar id is 204049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGXT	NM_000030.3	c.777-44A>G		intron_variant		ENST00000307503.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGXT	ENST00000307503.4	c.777-44A>G		intron_variant		1	NM_000030.3	P1
AGXT	ENST00000476698.1	n.429-44A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119110 AN: 151996 Hom.: 47604 Cov.: 34

Gnomad AFR AF: 0.949

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.734

Gnomad OTH AF: 0.748

GnomAD3 exomes AF: 0.716 AC: 177017 AN: 247316 Hom.: 64384 AF XY: 0.712 AC XY: 95218 AN XY: 133812

Gnomad AFR exome AF: 0.958

Gnomad AMR exome AF: 0.577

Gnomad ASJ exome AF: 0.731

Gnomad EAS exome AF: 0.769

Gnomad SAS exome AF: 0.626

Gnomad FIN exome AF: 0.744

Gnomad NFE exome AF: 0.732

Gnomad OTH exome AF: 0.722

GnomAD4 exome AF: 0.733 AC: 1060802 AN: 1447720 Hom.: 391003 Cov.: 32 AF XY: 0.729 AC XY: 525662 AN XY: 720890

Gnomad4 AFR exome AF: 0.958

Gnomad4 AMR exome AF: 0.589

Gnomad4 ASJ exome AF: 0.733

Gnomad4 EAS exome AF: 0.741

Gnomad4 SAS exome AF: 0.628

Gnomad4 FIN exome AF: 0.742

Gnomad4 NFE exome AF: 0.739

Gnomad4 OTH exome AF: 0.743

GnomAD4 genome AF: 0.784 AC: 119197 AN: 152112 Hom.: 47651 Cov.: 34 AF XY: 0.780 AC XY: 57965 AN XY: 74330

Gnomad4 AFR AF: 0.949

Gnomad4 AMR AF: 0.666

Gnomad4 ASJ AF: 0.726

Gnomad4 EAS AF: 0.751

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.748

Gnomad4 NFE AF: 0.734

Gnomad4 OTH AF: 0.741

Alfa AF: 0.753 Hom.: 8025

Bravo AF: 0.785

Asia WGS AF: 0.690 AC: 2403 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1 Benign:2

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:1

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	-0.94
Cadd	Benign	0.28
Dann	Benign	0.069
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs12464426; hg19: chr2-241815308; COSMIC: COSV56755419; COSMIC: COSV56755419;