chr2-240878099-A-G

Position:

chr2-240878099-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000030.3(AGXT):c.1020A>G(p.Ile340Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,613,084 control chromosomes in the GnomAD database, including 30,860 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2129 hom., cov: 33)

Exomes 𝑓: 0.19 ( 28731 hom. )

Consequence

AGXT
NM_000030.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:11O:1

Conservation

PhyloP100: 2.93

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022816956).

BP6

Variant 2-240878099-A-G is Benign according to our data. Variant chr2-240878099-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 39486.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240878099-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGXT	NM_000030.3 linkuse as main transcript	c.1020A>G	p.Ile340Met	missense_variant	10/11	ENST00000307503.4	NP_000021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGXT	ENST00000307503.4 linkuse as main transcript	c.1020A>G	p.Ile340Met	missense_variant	10/11	1	NM_000030.3	ENSP00000302620	P1
AGXT	ENST00000470255.1 linkuse as main transcript	n.798A>G		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

23240

AN:

152056

Hom.:

2127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0618

Gnomad AMI

AF:

0.248

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.189

Gnomad EAS

AF:

0.0751

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.242

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.204

Gnomad OTH

AF:

0.167

GnomAD3 exomes

AF:

0.164

AC:

41095

AN:

250624

Hom.:

3837

AF XY:

0.166

AC XY:

22450

AN XY:

135544

show subpopulations

Gnomad AFR exome

AF:

0.0629

Gnomad AMR exome

AF:

0.106

Gnomad ASJ exome

AF:

0.196

Gnomad EAS exome

AF:

0.0857

Gnomad SAS exome

AF:

0.102

Gnomad FIN exome

AF:

0.250

Gnomad NFE exome

AF:

0.206

Gnomad OTH exome

AF:

0.180

GnomAD4 exome

AF:

0.193

AC:

281700

AN:

1460910

Hom.:

28731

Cov.:

AF XY:

0.190

AC XY:

138282

AN XY:

726764

show subpopulations

Gnomad4 AFR exome

AF:

0.0617

Gnomad4 AMR exome

AF:

0.107

Gnomad4 ASJ exome

AF:

0.193

Gnomad4 EAS exome

AF:

0.0777

Gnomad4 SAS exome

AF:

0.106

Gnomad4 FIN exome

AF:

0.244

Gnomad4 NFE exome

AF:

0.210

Gnomad4 OTH exome

AF:

0.178

GnomAD4 genome

AF:

0.153

AC:

23245

AN:

152174

Hom.:

2129

Cov.:

AF XY:

0.152

AC XY:

11317

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0619

Gnomad4 AMR

AF:

0.136

Gnomad4 ASJ

AF:

0.189

Gnomad4 EAS

AF:

0.0751

Gnomad4 SAS

AF:

0.105

Gnomad4 FIN

AF:

0.242

Gnomad4 NFE

AF:

0.204

Gnomad4 OTH

AF:

0.165

Alfa

AF:

0.189

Hom.:

5764

Bravo

AF:

0.143

TwinsUK

AF:

0.214

AC:

793

ALSPAC

AF:

0.204

AC:

786

ESP6500AA

AF:

0.0640

AC:

282

ESP6500EA

AF:

0.208

AC:

1788

ExAC

AF:

0.164

AC:

19922

Asia WGS

AF:

0.0730

AC:

254

AN:

3478

EpiCase

AF:

0.206

EpiControl

AF:

0.202

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1Benign:11Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary hyperoxaluria, type I

Uncertain:1Benign:6Other:1

Benign, no assertion criteria provided	literature only	OMIM	Sep 01, 2004	- -
not provided, no classification provided	literature only	GeneReviews	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Nov 17, 2021	- -
Uncertain significance, no assertion criteria provided	in vitro	Clinical Biochemistry Laboratory, Health Services Laboratory	Nov 27, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Oct 30, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 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:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 07, 2018	This variant is associated with the following publications: (PMID: 1703535, 33457257, 24205397, 30341509, 28906061, 15802217) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 26, 2016	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.40

CADD

Benign

0.50

DANN

Benign

0.091

DEOGEN2

Benign

0.26

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.23

MetaRNN

Benign

0.0023

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-2.2

MutationTaster

Benign

1.0

PrimateAI

Benign

0.40

PROVEAN

Benign

3.2

REVEL

Benign

0.27

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.054

MPC

0.033

ClinPred

0.0076

GERP RS

2.2

Varity_R

0.32

gMVP

0.76

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over