chr2-240869375-C-T

Position:

• chr2-240869375-C-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.358+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,565,884 control chromosomes in the GnomAD database, including 28,390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1989 hom., cov: 33)
  • Exomes 𝑓: 0.19 (26401 hom.)
• Consequence: AGXT NM_000030.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:6
• Conservation: PhyloP100: -0.839

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=-0.86).
• BP6: Variant 2-240869375-C-T is Benign according to our data. Variant chr2-240869375-C-T is described in ClinVar as [Benign]. Clinvar id is 204032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240869375-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGXT	NM_000030.3	c.358+13C>T		intron_variant		ENST00000307503.4	NP_000021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGXT	ENST00000307503.4	c.358+13C>T		intron_variant		1	NM_000030.3	ENSP00000302620.3
AGXT	ENST00000472436.1	n.378+13C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22025 AN: 151678 Hom.: 1986 Cov.: 33

Gnomad AFR AF: 0.0627

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.000967

Gnomad SAS AF: 0.0732

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.162

GnomAD3 exomes AF: 0.146 AC: 30732 AN: 210064 Hom.: 2862 AF XY: 0.150 AC XY: 16742 AN XY: 111702

Gnomad AFR exome AF: 0.0629

Gnomad AMR exome AF: 0.0820

Gnomad ASJ exome AF: 0.188

Gnomad EAS exome AF: 0.000334

Gnomad SAS exome AF: 0.0703

Gnomad FIN exome AF: 0.247

Gnomad NFE exome AF: 0.203

Gnomad OTH exome AF: 0.173

GnomAD4 exome AF: 0.185 AC: 261660 AN: 1414088 Hom.: 26401 Cov.: 33 AF XY: 0.182 AC XY: 127017 AN XY: 696968

Gnomad4 AFR exome AF: 0.0642

Gnomad4 AMR exome AF: 0.0835

Gnomad4 ASJ exome AF: 0.177

Gnomad4 EAS exome AF: 0.000331

Gnomad4 SAS exome AF: 0.0755

Gnomad4 FIN exome AF: 0.233

Gnomad4 NFE exome AF: 0.206

Gnomad4 OTH exome AF: 0.169

GnomAD4 genome AF: 0.145 AC: 22030 AN: 151796 Hom.: 1989 Cov.: 33 AF XY: 0.143 AC XY: 10617 AN XY: 74176

Gnomad4 AFR AF: 0.0627

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.000969

Gnomad4 SAS AF: 0.0741

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.159

Alfa AF: 0.169 Hom.: 478

Bravo AF: 0.135

Asia WGS AF: 0.0330 AC: 116 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1 Benign:6

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	Illumina Laboratory Services, Illumina	Jan 13, 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. -
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:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 07, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.86
DANN	Benign	0.66

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: rs34995778; hg19: chr2-241808792; COSMIC: COSV56755317; COSMIC: COSV56755317;