Variant summary

Our verdict is Pathogenic. The variant received 13 ACMG points: 13P and 0B. PVS1PS1_ModeratePM2PP5

The NM_000030.3(AGXT):c.3G>T(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.00000754 in 1,458,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

AGXT
NM_000030.3 start_lost

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 4.14

Publications

0 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:

ENSG00000297735 (HGNC:):

ENSG00000297735 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 13 ACMG points.

PVS1

Start lost variant, next in-frame start position is after 24 pathogenic variants. Next in-frame start position is after 38 codons. Genomic position: 240868977. Lost 0.095 part of the original CDS.

PS1

Another start lost variant in NM_000030.3 (AGXT) was described as [Pathogenic] in ClinVar

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 2-240868868-G-T is Pathogenic according to our data. Variant chr2-240868868-G-T is described in ClinVar as Pathogenic. ClinVar VariationId is 204066.Status of the report is no_assertion_criteria_provided, 0 stars.

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.3G>T	p.Met1?	start_lost	Exon 1 of 11	NP_000021.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AGXT	ENST00000307503.4	TSL:1 MANE Select	c.3G>T	p.Met1?	start_lost	Exon 1 of 11	ENSP00000302620.3
AGXT	ENST00000472436.1	TSL:2	n.23G>T		non_coding_transcript_exon	Exon 1 of 5
ENSG00000297735	ENST00000750632.1		n.237+1365C>A		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000754

AC:

AN:

1458314

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

725284

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33434

American (AMR)

AF:

0.00

AC:

AN:

44420

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26068

East Asian (EAS)

AF:

0.00

AC:

AN:

39544

South Asian (SAS)

AF:

0.00

AC:

AN:

85766

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52028

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.00000900

AC:

AN:

1111094

Other (OTH)

AF:

0.0000166

AC:

AN:

60212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary hyperoxaluria, type I (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.62

BayesDel_noAF

Pathogenic

0.34

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

Eigen

Benign

0.18

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.89

MetaRNN

Pathogenic

0.99

MetaSVM

Uncertain

0.47

PhyloP100

4.1

PROVEAN

Benign

-1.4

REVEL

Pathogenic

0.71

Sift

Uncertain

0.014

Sift4G

Uncertain

0.017

Polyphen

0.83

Vest4

0.88

MutPred

1.0

Gain of sheet (P = 0.0266)

MVP

0.93

ClinPred

0.98

GERP RS

4.4

PromoterAI

-0.082

Neutral

(source)

Varity_R

0.50

gMVP

0.81

Mutation Taster

=11/189

disease causing (ClinVar)

(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

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over