rs34885252

Positions:

chr2-240868930-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.65A>G(p.Asn22Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00842 in 1,613,066 control chromosomes in the GnomAD database, including 415 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 Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 131 hom., cov: 33)

Exomes 𝑓: 0.0067 ( 284 hom. )

Consequence

AGXT
NM_000030.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:6

Conservation

PhyloP100: -0.240

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:

AGXT (HGNC:):

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=0.0016427934).

BP6

Variant 2-240868930-A-G is Benign according to our data. Variant chr2-240868930-A-G is described in ClinVar as [Benign]. Clinvar id is 204020.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0692 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.65A>G	p.Asn22Ser	missense_variant	1/11	ENST00000307503.4	NP_000021.1	P21549

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGXT	ENST00000307503.4 linkuse as main transcript	c.65A>G	p.Asn22Ser	missense_variant	1/11	1	NM_000030.3	ENSP00000302620.3		P21549
AGXT	ENST00000472436.1 linkuse as main transcript	n.85A>G		non_coding_transcript_exon_variant	1/5	2

Frequencies

GnomAD3 genomes

AF:

0.0245

AC:

3730

AN:

151972

Hom.:

131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0713

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00916

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.0718

Gnomad SAS

AF:

0.0300

Gnomad FIN

AF:

0.00123

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000824

Gnomad OTH

AF:

0.0206

GnomAD3 exomes

AF:

0.0167

AC:

4136

AN:

248228

Hom.:

127

AF XY:

0.0158

AC XY:

2123

AN XY:

134772

show subpopulations

Gnomad AFR exome

AF:

0.0719

Gnomad AMR exome

AF:

0.00825

Gnomad ASJ exome

AF:

0.00270

Gnomad EAS exome

AF:

0.0869

Gnomad SAS exome

AF:

0.0294

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.00101

Gnomad OTH exome

AF:

0.00869

GnomAD4 exome

AF:

0.00674

AC:

9842

AN:

1460976

Hom.:

284

Cov.:

AF XY:

0.00710

AC XY:

5161

AN XY:

726788

show subpopulations

Gnomad4 AFR exome

AF:

0.0725

Gnomad4 AMR exome

AF:

0.00836

Gnomad4 ASJ exome

AF:

0.00302

Gnomad4 EAS exome

AF:

0.0772

Gnomad4 SAS exome

AF:

0.0284

Gnomad4 FIN exome

AF:

0.000647

Gnomad4 NFE exome

AF:

0.000676

Gnomad4 OTH exome

AF:

0.0103

GnomAD4 genome

AF:

0.0246

AC:

3738

AN:

152090

Hom.:

131

Cov.:

AF XY:

0.0241

AC XY:

1795

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0713

Gnomad4 AMR

AF:

0.00915

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.0717

Gnomad4 SAS

AF:

0.0299

Gnomad4 FIN

AF:

0.00123

Gnomad4 NFE

AF:

0.000824

Gnomad4 OTH

AF:

0.0203

Alfa

AF:

0.00888

Hom.:

Bravo

AF:

0.0279

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.0697

AC:

307

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.0179

AC:

2175

Asia WGS

AF:

0.0410

AC:

143

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.00101

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary hyperoxaluria, type I

Uncertain:1Benign:2

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Oct 17, 2019	- -
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. -
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	Jan 18, 2019	This variant is associated with the following publications: (PMID: 28969594) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jun 22, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.0030

DANN

Benign

0.26

DEOGEN2

Benign

0.077

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.22

MetaRNN

Benign

0.0016

MetaSVM

Benign

-0.63

MutationAssessor

Benign

-0.27

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.010

REVEL

Benign

0.22

Sift

Benign

0.91

Sift4G

Benign

0.85

Polyphen

0.0

Vest4

0.026

MPC

0.029

ClinPred

0.00096

GERP RS

-8.8

Varity_R

0.043

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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