rs117195882

Positions:

chr2-240873011-C-T

Variant summary

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

The NM_000030.3(AGXT):c.557C>T(p.Ala186Val) variant causes a missense change. The variant allele was found at a frequency of 0.00453 in 1,613,864 control chromosomes in the GnomAD database, including 207 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 22 hom., cov: 32)

Exomes 𝑓: 0.0046 ( 185 hom. )

Consequence

AGXT
NM_000030.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 4.09

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 (MetaRNN=0.01129064).

BP6

Variant 2-240873011-C-T is Benign according to our data. Variant chr2-240873011-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 92311.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240873011-C-T is described in Lovd as [Likely_pathogenic].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0659 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.557C>T	p.Ala186Val	missense_variant	5/11	ENST00000307503.4	NP_000021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
AGXT	ENST00000307503.4 linkuse as main transcript	c.557C>T	p.Ala186Val	missense_variant	5/11	1	NM_000030.3	ENSP00000302620	P1
AGXT	ENST00000472436.1 linkuse as main transcript	n.577C>T		non_coding_transcript_exon_variant	5/5	2
AGXT	ENST00000476698.1 linkuse as main transcript	n.294C>T		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes

AF:

0.00410

AC:

624

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0719

Gnomad SAS

AF:

0.0298

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.0113

AC:

2811

AN:

249728

Hom.:

AF XY:

0.0119

AC XY:

1613

AN XY:

135090

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00521

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.0868

Gnomad SAS exome

AF:

0.0292

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.000883

Gnomad OTH exome

AF:

0.00473

GnomAD4 exome

AF:

0.00457

AC:

6684

AN:

1461584

Hom.:

185

Cov.:

AF XY:

0.00527

AC XY:

3835

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00483

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0768

Gnomad4 SAS exome

AF:

0.0281

Gnomad4 FIN exome

AF:

0.000694

Gnomad4 NFE exome

AF:

0.000564

Gnomad4 OTH exome

AF:

0.00525

GnomAD4 genome

AF:

0.00408

AC:

622

AN:

152280

Hom.:

Cov.:

AF XY:

0.00496

AC XY:

369

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00189

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0719

Gnomad4 SAS

AF:

0.0296

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.000916

Hom.:

Bravo

AF:

0.00413

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.0114

AC:

1384

Asia WGS

AF:

0.0370

AC:

129

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000711

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary hyperoxaluria, type I

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Apr 16, 2022	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Nov 15, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Likely benign, criteria provided, single submitter	clinical testing	Clinical Biochemistry Laboratory, Health Services Laboratory	Oct 27, 2023	Found in cis with c.590G>A in 2 unrelated individuals. ACMG:PM2 PP3 BP2 BP5 -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 07, 2020	This variant is associated with the following publications: (PMID: 30341509, 33457257) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Aug 24, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.88

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.37

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.79

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.45

MutationAssessor

Pathogenic

3.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.4

REVEL

Uncertain

0.61

Sift

Benign

0.089

Sift4G

Uncertain

0.040

Polyphen

0.45

Vest4

0.15

MPC

0.055

ClinPred

0.069

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.60

gMVP

0.92

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