rs12695032

Variant names:

• chr2-240876056-G-A
• rs12695032
• NM_000030.3:c.846+52G>A

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.846+52G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 1,593,468 control chromosomes in the GnomAD database, including 229,072 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (16303 hom., cov: 34)
  • Exomes 𝑓: 0.53 (212769 hom.)
• Consequence: AGXT NM_000030.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:3
• Conservation: PhyloP100: -1.96
• Publications: 5 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=-0.85).
• BP6: Variant 2-240876056-G-A is Benign according to our data. Variant chr2-240876056-G-A is described in ClinVar as Benign. ClinVar VariationId is 204054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGXT	NM_000030.3	c.846+52G>A		intron_variant	Intron 8 of 10	ENST00000307503.4	NP_000021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGXT	ENST00000307503.4	c.846+52G>A		intron_variant	Intron 8 of 10	1	NM_000030.3	ENSP00000302620.3
AGXT	ENST00000476698.1	n.*43G>A		downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65518 AN: 151994 Hom.: 16307 Cov.: 34

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.447

GnomAD2 exomes AF: 0.474 AC: 113347 AN: 239088 AF XY: 0.482

Gnomad AFR exome AF: 0.192

Gnomad AMR exome AF: 0.340

Gnomad ASJ exome AF: 0.428

Gnomad EAS exome AF: 0.334

Gnomad FIN exome AF: 0.636

Gnomad NFE exome AF: 0.573

Gnomad OTH exome AF: 0.506

GnomAD4 exome AF: 0.535 AC: 770956 AN: 1441356 Hom.: 212769 Cov.: 31 AF XY: 0.532 AC XY: 381519 AN XY: 717402

African (AFR) AF: 0.186 AC: 6097 AN: 32800

American (AMR) AF: 0.349 AC: 15258 AN: 43730

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 11035 AN: 25940

East Asian (EAS) AF: 0.312 AC: 12199 AN: 39092

South Asian (SAS) AF: 0.389 AC: 32991 AN: 84794

European-Finnish (FIN) AF: 0.632 AC: 33519 AN: 53012

Middle Eastern (MID) AF: 0.423 AC: 2419 AN: 5724

European-Non Finnish (NFE) AF: 0.572 AC: 627802 AN: 1096608

Other (OTH) AF: 0.497 AC: 29636 AN: 59656

GnomAD4 genome AF: 0.431 AC: 65516 AN: 152112 Hom.: 16303 Cov.: 34 AF XY: 0.429 AC XY: 31934 AN XY: 74358

African (AFR) AF: 0.192 AC: 7982 AN: 41492

American (AMR) AF: 0.379 AC: 5794 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1425 AN: 3472

East Asian (EAS) AF: 0.321 AC: 1658 AN: 5164

South Asian (SAS) AF: 0.367 AC: 1768 AN: 4820

European-Finnish (FIN) AF: 0.647 AC: 6835 AN: 10566

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.565 AC: 38443 AN: 67988

Other (OTH) AF: 0.445 AC: 942 AN: 2116

Alfa AF: 0.472 Hom.: 18415

Bravo AF: 0.405

Asia WGS AF: 0.346 AC: 1206 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

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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	-0.85
CADD	Benign	0.11
DANN	Benign	0.58
PhyloP100		-2.0
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: rs12695032; hg19: chr2-241815473;