rs147601535

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7

The NM_000030.3(AGXT):​c.489G>A​(p.Leu163Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 1,599,146 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).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

AGXT
NM_000030.3 synonymous

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:4

Conservation

PhyloP100: -0.372
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
Variant 2-240871414-G-A is Benign according to our data. Variant chr2-240871414-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 204040.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-0.372 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AGXTNM_000030.3 linkc.489G>A p.Leu163Leu synonymous_variant Exon 4 of 11 ENST00000307503.4 NP_000021.1 P21549

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AGXTENST00000307503.4 linkc.489G>A p.Leu163Leu synonymous_variant Exon 4 of 11 1 NM_000030.3 ENSP00000302620.3 P21549
AGXTENST00000472436.1 linkn.509G>A non_coding_transcript_exon_variant Exon 4 of 5 2
AGXTENST00000476698.1 linkn.226G>A non_coding_transcript_exon_variant Exon 1 of 4 5

Frequencies

GnomAD3 genomes
AF:
0.000177
AC:
27
AN:
152192
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000206
AC:
46
AN:
223138
Hom.:
0
AF XY:
0.000215
AC XY:
26
AN XY:
120654
show subpopulations
Gnomad AFR exome
AF:
0.000291
Gnomad AMR exome
AF:
0.0000935
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000221
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000291
Gnomad OTH exome
AF:
0.000724
GnomAD4 exome
AF:
0.000211
AC:
305
AN:
1446954
Hom.:
1
Cov.:
31
AF XY:
0.000202
AC XY:
145
AN XY:
718344
show subpopulations
Gnomad4 AFR exome
AF:
0.0000902
Gnomad4 AMR exome
AF:
0.0000932
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000216
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000221
Gnomad4 OTH exome
AF:
0.000451
GnomAD4 genome
AF:
0.000177
AC:
27
AN:
152192
Hom.:
0
Cov.:
33
AF XY:
0.000108
AC XY:
8
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.000169
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000197
Hom.:
0
Bravo
AF:
0.000181

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:4
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Primary hyperoxaluria, type I Uncertain:1Benign:1
Nov 27, 2014
Clinical Biochemistry Laboratory, Health Services Laboratory
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: research

- -

May 02, 2020
Natera, Inc.
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

not provided Benign:2
Dec 23, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Jan 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

AGXT: BP4, BP7 -

Primary hyperoxaluria Uncertain:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not specified Benign:1
-
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.64
CADD
Benign
7.0
DANN
Benign
0.74
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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.

Other links and lift over

dbSNP: rs147601535; hg19: chr2-241810831; COSMIC: COSV56753287; API