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. 16/21 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

Publications

8 publications found

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 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

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, 9 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 alanine glyoxylate aminotransferase deficiency, primary hyperoxaluria type 1.

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 Benign/Likely_benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000030.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGXT	NM_000030.3	MANE Select	c.883G>A	p.Ala295Thr	missense	Exon 9 of 11	NP_000021.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGXT	ENST00000307503.4	TSL:1 MANE Select	c.883G>A	p.Ala295Thr	missense	Exon 9 of 11	ENSP00000302620.3
	AGXT	ENST00000470255.1	TSL:2	n.661G>A		non_coding_transcript_exon	Exon 1 of 3

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

African (AFR)

AF:

0.0813

AC:

2570

AN:

31598

American (AMR)

AF:

0.00409

AC:

146

AN:

35676

Ashkenazi Jewish (ASJ)

AF:

0.0218

AC:

548

AN:

25160

East Asian (EAS)

AF:

0.000196

AC:

AN:

35744

South Asian (SAS)

AF:

0.000202

AC:

AN:

79222

European-Finnish (FIN)

AF:

0.0000206

AC:

AN:

48520

Middle Eastern (MID)

AF:

0.00316

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.000472

AC:

509

AN:

1078866

Other (OTH)

AF:

0.00691

AC:

401

AN:

57992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

214

428

641

855

1069

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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

African (AFR)

AF:

0.0776

AC:

3224

AN:

41566

American (AMR)

AF:

0.00718

AC:

110

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0202

AC:

AN:

3472

East Asian (EAS)

AF:

0.000965

AC:

AN:

5184

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000573

AC:

AN:

68024

Other (OTH)

AF:

0.0189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

157

314

471

628

785

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary hyperoxaluria, type I (5)

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.30

CADD

Benign

0.85

(source)

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

PhyloP100

0.0010

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)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over