NM_000030.3:c.*19G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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: Ambry Genetics, G2P, Orphanet, Labcorp Genetics (formerly Invitae), Myriad Women’s Health

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 46 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000030.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGXT	NM_000030.3	MANE Select	c.*19G>A		3_prime_UTR	Exon 11 of 11	NP_000021.1	P21549

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGXT	ENST00000307503.4	TSL:1 MANE Select	c.*19G>A		3_prime_UTR	Exon 11 of 11	ENSP00000302620.3	P21549
	AGXT	ENST00000908235.1		c.*19G>A		3_prime_UTR	Exon 12 of 12	ENSP00000578294.1
	AGXT	ENST00000908236.1		c.*19G>A		3_prime_UTR	Exon 12 of 12	ENSP00000578295.1

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

GnomAD2 exomes AF: 0.00391 AC: 686 AN: 175302 AF XY: 0.00401

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 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

African (AFR) AF: 0.000886 AC: 29 AN: 32714

American (AMR) AF: 0.00182 AC: 68 AN: 37438

Ashkenazi Jewish (ASJ) AF: 0.00340 AC: 86 AN: 25268

East Asian (EAS) AF: 0.00 AC: 0 AN: 37892

South Asian (SAS) AF: 0.0000498 AC: 4 AN: 80372

European-Finnish (FIN) AF: 0.00316 AC: 145 AN: 45948

Middle Eastern (MID) AF: 0.000351 AC: 2 AN: 5702

European-Non Finnish (NFE) AF: 0.00782 AC: 8504 AN: 1087964

Other (OTH) AF: 0.00526 AC: 309 AN: 58782

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

African (AFR) AF: 0.00128 AC: 53 AN: 41568

American (AMR) AF: 0.00190 AC: 29 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00414 AC: 44 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00657 AC: 447 AN: 68016

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00456 Hom.: 0

Bravo AF: 0.00365

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	1	Primary hyperoxaluria, type I (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.65
PhyloP100		0.048
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

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: rs143458283; hg19: chr2-241818257;