2-240869375-C-T

Variant names:

• chr2-240869375-C-T
• rs34995778
• NM_000030.3:c.358+13C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• alanine glyoxylate aminotransferase deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• primary hyperoxaluria type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Myriad Women’s Health, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000297735 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 204032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGXT	NM_000030.3	c.358+13C>T		intron_variant	Intron 2 of 10	ENST00000307503.4	NP_000021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGXT	ENST00000307503.4	c.358+13C>T		intron_variant	Intron 2 of 10	1	NM_000030.3	ENSP00000302620.3

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

GnomAD2 exomes AF: 0.146 AC: 30732 AN: 210064 AF XY: 0.150

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 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

African (AFR) AF: 0.0642 AC: 2097 AN: 32654

American (AMR) AF: 0.0835 AC: 3475 AN: 41620

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 4050 AN: 22894

East Asian (EAS) AF: 0.000331 AC: 13 AN: 39276

South Asian (SAS) AF: 0.0755 AC: 5900 AN: 78172

European-Finnish (FIN) AF: 0.233 AC: 11589 AN: 49834

Middle Eastern (MID) AF: 0.165 AC: 868 AN: 5246

European-Non Finnish (NFE) AF: 0.206 AC: 223804 AN: 1086078

Other (OTH) AF: 0.169 AC: 9864 AN: 58314

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

African (AFR) AF: 0.0627 AC: 2604 AN: 41520

American (AMR) AF: 0.119 AC: 1823 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 619 AN: 3468

East Asian (EAS) AF: 0.000969 AC: 5 AN: 5158

South Asian (SAS) AF: 0.0741 AC: 354 AN: 4778

European-Finnish (FIN) AF: 0.231 AC: 2426 AN: 10500

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13604 AN: 67818

Other (OTH) AF: 0.159 AC: 333 AN: 2090

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

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Nov 27, 2014

Clinical Biochemistry Laboratory, Health Services Laboratory

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

- -

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 07, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.86
DANN	Benign	0.66
PhyloP100		-0.84
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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