rs143458283

Variant names:

• chr2-240878840-G-A
• rs143458283
• NM_000030.3:c.*19G>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000030.3(AGXT):​c.*19G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00622 in 1,564,384 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0065 (46 hom.)
• Consequence: AGXT NM_000030.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: 0.0480

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 2-240878840-G-A is Benign according to our data. Variant chr2-240878840-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 204062.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00387 (590/152304) while in subpopulation NFE AF= 0.00657 (447/68016). AF 95% confidence interval is 0.00607. There are 1 homozygotes in gnomad4. There are 277 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 46 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGXT	NM_000030.3	c.*19G>A		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.*19G>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_000030.3	ENSP00000302620.3
AGXT	ENST00000470255.1	n.976G>A		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes AF: 0.00388 AC: 591 AN: 152186 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00414

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00657

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00391 AC: 686 AN: 175302 Hom.: 3 AF XY: 0.00401 AC XY: 376 AN XY: 93738

Gnomad AFR exome AF: 0.00112

Gnomad AMR exome AF: 0.00168

Gnomad ASJ exome AF: 0.00322

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000418

Gnomad FIN exome AF: 0.00421

Gnomad NFE exome AF: 0.00709

Gnomad OTH exome AF: 0.00358

GnomAD4 exome AF: 0.00648 AC: 9147 AN: 1412080 Hom.: 46 Cov.: 31 AF XY: 0.00624 AC XY: 4363 AN XY: 698724

Gnomad4 AFR exome AF: 0.000886

Gnomad4 AMR exome AF: 0.00182

Gnomad4 ASJ exome AF: 0.00340

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000498

Gnomad4 FIN exome AF: 0.00316

Gnomad4 NFE exome AF: 0.00782

Gnomad4 OTH exome AF: 0.00526

GnomAD4 genome AF: 0.00387 AC: 590 AN: 152304 Hom.: 1 Cov.: 33 AF XY: 0.00372 AC XY: 277 AN XY: 74466

Gnomad4 AFR AF: 0.00128

Gnomad4 AMR AF: 0.00190

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00414

Gnomad4 NFE AF: 0.00657

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00456 Hom.: 0

Bravo AF: 0.00365

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary hyperoxaluria, type I Uncertain:1 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs143458283; hg19: chr2-241818257;