rs13408961

Positions:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.023 ( 132 hom., cov: 34)

Exomes 𝑓: 0.0030 ( 112 hom. )

Consequence

AGXT
NM_000030.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications 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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

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 [Conflicting_classifications_of_pathogenicity]. Clinvar id is 204056.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=5, Uncertain_significance=1}.

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/exons	MANE	Protein	UniProt
AGXT	NM_000030.3 linkuse as main transcript	c.883G>A	p.Ala295Thr	missense_variant	9/11	ENST00000307503.4	NP_000021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGXT	ENST00000307503.4 linkuse as main transcript	c.883G>A	p.Ala295Thr	missense_variant	9/11	1	NM_000030.3	ENSP00000302620	P1
AGXT	ENST00000470255.1 linkuse as main transcript	n.661G>A		non_coding_transcript_exon_variant	1/3	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

GnomAD3 exomes

AF:

0.00667

AC:

1025

AN:

153624

Hom.:

AF XY:

0.00515

AC XY:

418

AN XY:

81130

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 SAS exome

AF:

0.0000878

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

Gnomad4 AMR exome

AF:

0.00409

Gnomad4 ASJ exome

AF:

0.0218

Gnomad4 EAS exome

AF:

0.000196

Gnomad4 SAS exome

AF:

0.000202

Gnomad4 FIN exome

AF:

0.0000206

Gnomad4 NFE exome

AF:

0.000472

Gnomad4 OTH exome

AF:

0.00691

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

Gnomad4 AMR

AF:

0.00718

Gnomad4 ASJ

AF:

0.0202

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000573

Gnomad4 OTH

AF:

0.0189

Alfa

AF:

0.00555

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: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:7

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Primary hyperoxaluria, type I

Uncertain:2Benign:3

Uncertain significance, no assertion criteria provided	research	Clinical Biochemistry Laboratory, Health Services Laboratory	Nov 27, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Sep 22, 2023	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Uncertain significance, criteria provided, single submitter	research	Center for Precision Medicine, Vanderbilt University Medical Center	Mar 16, 2018	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Sep 01, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 05, 2020	This variant is associated with the following publications: (PMID: 28492530, 29590070, 27884173, 24205397) -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

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

Feb 17, 2022

- -

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

MutationTaster

Benign

1.0

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

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