rs13408961

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 3P and 20B. PM1PP2BP4_StrongBP6_Very_StrongBA1

The NM_000030.3(AGXT):c.883G>A(p.Ala295Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00497 in 1,550,806 control chromosomes in the GnomAD database, including 244 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A295A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.023 ( 132 hom., cov: 34)

Exomes 𝑓: 0.0030 ( 112 hom. )

Consequence

AGXT
NM_000030.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:2B:7

Conservation

PhyloP100: 0.00100

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 was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

PM1

In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 6 uncertain in NM_000030.3

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 130 curated pathogenic missense variants (we use a threshold of 10). The gene has 12 curated benign missense variants. Gene score misZ: -0.26789 (below the threshold of 3.09). Trascript score misZ: -0.48778 (below the threshold of 3.09). GenCC associations: The gene is linked to primary hyperoxaluria type 1, alanine glyoxylate aminotransferase deficiency.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019549727).

BP6

Variant 2-240877573-G-A is Benign according to our data. Variant chr2-240877573-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 204056.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGXT	NM_000030.3 link	c.883G>A	p.Ala295Thr	missense_variant	Exon 9 of 11	ENST00000307503.4	NP_000021.1	P21549

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGXT	ENST00000307503.4 link	c.883G>A	p.Ala295Thr	missense_variant	Exon 9 of 11	1	NM_000030.3	ENSP00000302620.3		P21549
AGXT	ENST00000470255.1 link	n.661G>A		non_coding_transcript_exon_variant	Exon 1 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.0229

AC:

3479

AN:

152214

Hom.:

132

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0775

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00719

Gnomad ASJ

AF:

0.0202

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.0191

GnomAD2 exomes

AF:

0.00667

AC:

1025

AN:

153624

AF XY:

0.00515

show subpopulations

Gnomad AFR exome

AF:

0.0838

Gnomad AMR exome

AF:

0.00340

Gnomad ASJ exome

AF:

0.0203

Gnomad EAS exome

AF:

0.000267

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000634

Gnomad OTH exome

AF:

0.00436

GnomAD4 exome

AF:

0.00301

AC:

4216

AN:

1398474

Hom.:

112

Cov.:

AF XY:

0.00273

AC XY:

1886

AN XY:

689798

show subpopulations

Gnomad4 AFR exome

AF:

0.0813

AC:

2570

AN:

31598

Gnomad4 AMR exome

AF:

0.00409

AC:

146

AN:

35676

Gnomad4 ASJ exome

AF:

0.0218

AC:

548

AN:

25160

Gnomad4 EAS exome

AF:

0.000196

AC:

AN:

35744

Gnomad4 SAS exome

AF:

0.000202

AC:

AN:

79222

Gnomad4 FIN exome

AF:

0.0000206

AC:

AN:

48520

Gnomad4 NFE exome

AF:

0.000472

AC:

509

AN:

1078866

Gnomad4 Remaining exome

AF:

0.00691

AC:

401

AN:

57992

Heterozygous variant carriers

214

428

641

855

1069

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

196

294

392

490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0229

AC:

3492

AN:

152332

Hom.:

132

Cov.:

AF XY:

0.0221

AC XY:

1644

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0776

AC:

0.0775634

AN:

0.0775634

Gnomad4 AMR

AF:

0.00718

AC:

0.00718391

AN:

0.00718391

Gnomad4 ASJ

AF:

0.0202

AC:

0.0201613

AN:

0.0201613

Gnomad4 EAS

AF:

0.000965

AC:

0.000964506

AN:

0.000964506

Gnomad4 SAS

AF:

0.000414

AC:

0.000414079

AN:

0.000414079

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000573

AC:

0.000573327

AN:

0.000573327

Gnomad4 OTH

AF:

0.0189

AC:

0.0189215

AN:

0.0189215

Heterozygous variant carriers

157

314

471

628

785

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00650

Hom.:

Bravo

AF:

0.0261

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.0665

AC:

273

ESP6500EA

AF:

0.00138

AC:

ExAC

AF:

0.00498

AC:

377

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:2Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary hyperoxaluria, type I

Uncertain:2Benign:3

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. -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 16, 2018

Center for Precision Medicine, Vanderbilt University Medical Center

Significance:Uncertain significance

Review Status:flagged submission

Collection Method:research

- -

Nov 27, 2014

Clinical Biochemistry Laboratory, Health Services Laboratory

Significance:Uncertain significance

Review Status:flagged submission

Collection Method:research

- -

Sep 22, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Sep 01, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 05, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 28492530, 29590070, 27884173, 24205397) -

Jan 22, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Feb 17, 2022

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.30

CADD

Benign

0.85

DANN

Benign

0.91

DEOGEN2

Uncertain

0.46

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0020

MetaSVM

Benign

-0.72

MutationAssessor

Benign

0.97

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.1

REVEL

Benign

0.22

Sift

Benign

0.26

Sift4G

Benign

0.25

Polyphen

0.0050

Vest4

0.15

MVP

0.40

MPC

0.033

ClinPred

0.0073

GERP RS

-6.1

Varity_R

0.19

gMVP

0.85

Mutation Taster

=90/10

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

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