rs4675792

Variant names:

• chr2-240880109-C-T
• rs4675792
• NM_000030.3:c.*1288C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000030.3(AGXT):​c.*1288C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 152,018 control chromosomes in the GnomAD database, including 21,548 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.52 (21545 hom., cov: 32)
  • Exomes 𝑓: 1.0 (3 hom.)
• Consequence: AGXT NM_000030.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGXT	NM_000030.3	c.*1288C>T		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.*1288C>T		3_prime_UTR_variant	Exon 11 of 11	1	NM_000030.3	ENSP00000302620.3
AGXT	ENST00000470255.1	n.2245C>T		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78872 AN: 151894 Hom.: 21538 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.528

GnomAD4 exome AF: 1.00 AC: 6 AN: 6 Hom.: 3 Cov.: 0 AF XY: 1.00 AC XY: 4 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 4 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.519 AC: 78905 AN: 152012 Hom.: 21545 Cov.: 32 AF XY: 0.518 AC XY: 38517 AN XY: 74322

African (AFR) AF: 0.355 AC: 14703 AN: 41422

American (AMR) AF: 0.487 AC: 7433 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1666 AN: 3466

East Asian (EAS) AF: 0.586 AC: 3041 AN: 5186

South Asian (SAS) AF: 0.394 AC: 1897 AN: 4820

European-Finnish (FIN) AF: 0.678 AC: 7173 AN: 10572

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41148 AN: 67960

Other (OTH) AF: 0.524 AC: 1105 AN: 2108

Alfa AF: 0.560 Hom.: 56767

Bravo AF: 0.501

Asia WGS AF: 0.472 AC: 1645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.48
PhyloP100		-0.20

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4675792; hg19: chr2-241819526;