Genetic Variant AGXT:c.777-44A>G (chr2-240875891-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000030.3(AGXT):c.777-44A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 1,599,832 control chromosomes in the GnomAD database, including 438,654 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.78 ( 47651 hom., cov: 34)

Exomes 𝑓: 0.73 ( 391003 hom. )

Consequence

AGXT
NM_000030.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:3

Conservation

PhyloP100: -5.24

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 2-240875891-A-G is Benign according to our data. Variant chr2-240875891-A-G is described in ClinVar as [Benign]. Clinvar id is 204049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGXT	NM_000030.3 link	c.777-44A>G		intron_variant	Intron 7 of 10	ENST00000307503.4	NP_000021.1	P21549

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGXT	ENST00000307503.4 link	c.777-44A>G		intron_variant	Intron 7 of 10	1	NM_000030.3	ENSP00000302620.3		P21549
AGXT	ENST00000476698.1 link	n.429-44A>G		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.784

AC:

119110

AN:

151996

Hom.:

47604

Cov.:

show subpopulations

Gnomad AFR

AF:

0.949

Gnomad AMI

AF:

0.689

Gnomad AMR

AF:

0.666

Gnomad ASJ

AF:

0.726

Gnomad EAS

AF:

0.752

Gnomad SAS

AF:

0.625

Gnomad FIN

AF:

0.748

Gnomad MID

AF:

0.709

Gnomad NFE

AF:

0.734

Gnomad OTH

AF:

0.748

GnomAD3 exomes

AF:

0.716

AC:

177017

AN:

247316

Hom.:

64384

AF XY:

0.712

AC XY:

95218

AN XY:

133812

show subpopulations

Gnomad AFR exome

AF:

0.958

Gnomad AMR exome

AF:

0.577

Gnomad ASJ exome

AF:

0.731

Gnomad EAS exome

AF:

0.769

Gnomad SAS exome

AF:

0.626

Gnomad FIN exome

AF:

0.744

Gnomad NFE exome

AF:

0.732

Gnomad OTH exome

AF:

0.722

GnomAD4 exome

AF:

0.733

AC:

1060802

AN:

1447720

Hom.:

391003

Cov.:

AF XY:

0.729

AC XY:

525662

AN XY:

720890

show subpopulations

Gnomad4 AFR exome

AF:

0.958

Gnomad4 AMR exome

AF:

0.589

Gnomad4 ASJ exome

AF:

0.733

Gnomad4 EAS exome

AF:

0.741

Gnomad4 SAS exome

AF:

0.628

Gnomad4 FIN exome

AF:

0.742

Gnomad4 NFE exome

AF:

0.739

Gnomad4 OTH exome

AF:

0.743

GnomAD4 genome

AF:

0.784

AC:

119197

AN:

152112

Hom.:

47651

Cov.:

AF XY:

0.780

AC XY:

57965

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.949

Gnomad4 AMR

AF:

0.666

Gnomad4 ASJ

AF:

0.726

Gnomad4 EAS

AF:

0.751

Gnomad4 SAS

AF:

0.625

Gnomad4 FIN

AF:

0.748

Gnomad4 NFE

AF:

0.734

Gnomad4 OTH

AF:

0.741

Alfa

AF:

0.753

Hom.:

8025

Bravo

AF:

0.785

Asia WGS

AF:

0.690

AC:

2403

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, multiple submitters, no conflicts

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

- -

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Aug 07, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.28

DANN

Benign

0.069

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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