rs61729604

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 3P and 4B. PM1PP2BP4_Strong

The NM_000030.3(AGXT):c.866G>A(p.Arg289His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000503 in 1,549,970 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R289C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00042 ( 1 hom. )

Consequence

AGXT
NM_000030.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:9B:1

Conservation

PhyloP100: -0.494

Publications

10 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, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Ambry Genetics, Orphanet

AGXT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM1

In a hotspot region, there are 4 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 7 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=0.009120911).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGXT	NM_000030.3	MANE Select	c.866G>A	p.Arg289His	missense	Exon 9 of 11	NP_000021.1	P21549

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AGXT	ENST00000307503.4	TSL:1 MANE Select	c.866G>A	p.Arg289His	missense	Exon 9 of 11	ENSP00000302620.3	P21549
AGXT	ENST00000908235.1		c.1139G>A	p.Arg380His	missense	Exon 10 of 12	ENSP00000578294.1
AGXT	ENST00000908236.1		c.1055G>A	p.Arg352His	missense	Exon 10 of 12	ENSP00000578295.1

Frequencies

GnomAD3 genomes

AF:

0.00130

AC:

198

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00304

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.000980

AC:

150

AN:

153122

AF XY:

0.000952

show subpopulations

Gnomad AFR exome

AF:

0.00360

Gnomad AMR exome

AF:

0.00138

Gnomad ASJ exome

AF:

0.00618

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000394

Gnomad OTH exome

AF:

0.00231

GnomAD4 exome

AF:

0.000416

AC:

582

AN:

1397628

Hom.:

Cov.:

AF XY:

0.000406

AC XY:

280

AN XY:

689272

show subpopulations

African (AFR)

AF:

0.00348

AC:

110

AN:

31580

American (AMR)

AF:

0.00143

AC:

AN:

35602

Ashkenazi Jewish (ASJ)

AF:

0.00601

AC:

151

AN:

25110

East Asian (EAS)

AF:

0.000140

AC:

AN:

35724

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79108

European-Finnish (FIN)

AF:

0.0000206

AC:

AN:

48518

Middle Eastern (MID)

AF:

0.00211

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.000181

AC:

195

AN:

1078350

Other (OTH)

AF:

0.000966

AC:

AN:

57946

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

132

165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.00130

AC:

198

AN:

152342

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.00303

AC:

126

AN:

41578

American (AMR)

AF:

0.00183

AC:

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.00634

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000221

AC:

AN:

68022

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000772

Hom.:

Bravo

AF:

0.00175

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00173

AC:

ESP6500EA

AF:

0.000256

AC:

ExAC

AF:

0.000409

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Primary hyperoxaluria, type I (4)

Alanine glyoxylate aminotransferase deficiency (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.54

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.81

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.0091

MetaSVM

Uncertain

-0.095

MutationAssessor

Uncertain

2.2

PhyloP100

-0.49

PrimateAI

Benign

0.30

PROVEAN

Benign

-2.3

REVEL

Uncertain

0.56

Sift

Benign

0.076

Sift4G

Benign

0.12

Polyphen

0.0040

Vest4

0.095

MVP

0.86

MPC

0.037

ClinPred

0.0078

GERP RS

-0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.76

Mutation Taster

=56/44

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

Computational scores

Splicing

Publications

Other links and lift over