rs4344931

Variant names:

• chr2-240879110-A-C
• rs4344931
• NM_000030.3:c.*289A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-240879110-A-C
• chr2-240879110-A-G
• chr2-240879110-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000030.3(AGXT):​c.*289A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 532,554 control chromosomes in the GnomAD database, including 130,757 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (40986 hom., cov: 32)
  • Exomes 𝑓: 0.68 (89771 hom.)
• Consequence: AGXT NM_000030.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:3
• Conservation: PhyloP100: -3.97
• Publications: 23 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-240879110-A-C is Benign according to our data. Variant chr2-240879110-A-C is described in ClinVar as Benign. ClinVar VariationId is 204064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGXT	NM_000030.3	c.*289A>C		3_prime_UTR_variant	Exon 11 of 11	ENST00000307503.4	NP_000021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGXT	ENST00000307503.4	c.*289A>C		3_prime_UTR_variant	Exon 11 of 11	1	NM_000030.3	ENSP00000302620.3
AGXT	ENST00000470255.1	n.1246A>C		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110609 AN: 151960 Hom.: 40945 Cov.: 32

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.696

GnomAD4 exome AF: 0.683 AC: 259740 AN: 380478 Hom.: 89771 Cov.: 0 AF XY: 0.673 AC XY: 134824 AN XY: 200188

African (AFR) AF: 0.849 AC: 9337 AN: 10998

American (AMR) AF: 0.558 AC: 9083 AN: 16290

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 7094 AN: 11698

East Asian (EAS) AF: 0.723 AC: 18205 AN: 25192

South Asian (SAS) AF: 0.544 AC: 24162 AN: 44452

European-Finnish (FIN) AF: 0.738 AC: 16849 AN: 22832

Middle Eastern (MID) AF: 0.619 AC: 1007 AN: 1628

European-Non Finnish (NFE) AF: 0.705 AC: 158817 AN: 225390

Other (OTH) AF: 0.690 AC: 15186 AN: 21998

GnomAD4 genome AF: 0.728 AC: 110697 AN: 152076 Hom.: 40986 Cov.: 32 AF XY: 0.723 AC XY: 53712 AN XY: 74332

African (AFR) AF: 0.852 AC: 35346 AN: 41504

American (AMR) AF: 0.592 AC: 9048 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 2059 AN: 3472

East Asian (EAS) AF: 0.736 AC: 3795 AN: 5154

South Asian (SAS) AF: 0.534 AC: 2570 AN: 4814

European-Finnish (FIN) AF: 0.745 AC: 7895 AN: 10594

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.702 AC: 47714 AN: 67948

Other (OTH) AF: 0.690 AC: 1452 AN: 2104

Alfa AF: 0.705 Hom.: 76812

Bravo AF: 0.724

Asia WGS AF: 0.653 AC: 2276 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1 Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary hyperoxaluria, type I Uncertain:1 Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Nov 27, 2014

Clinical Biochemistry Laboratory, Health Services Laboratory

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

- -

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	-0.91
CADD	Benign	0.16
DANN	Benign	0.47
PhyloP100		-4.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4344931; hg19: chr2-241818527;