rs180177209

Positions:

• chr2-240869408-AGGCCTCCCT-A
• chr2-240869408-AGGCCTCCCT-AGGCCTCCCTGGCCTCCCT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000030.3(AGXT):​c.358+56_358+64delGGCCTCCCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 1,513,548 control chromosomes in the GnomAD database, including 99,617 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (7370 hom., cov: 17)
  • Exomes 𝑓: 0.36 (92247 hom.)
• Consequence: AGXT NM_000030.3 intron
• Clinical Significance: Benign criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: -0.161

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-240869408-AGGCCTCCCT-A is Benign according to our data. Variant chr2-240869408-AGGCCTCCCT-A is described in ClinVar as [Benign]. Clinvar id is 204033.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGXT	NM_000030.3	c.358+56_358+64delGGCCTCCCT		intron_variant		ENST00000307503.4	NP_000021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGXT	ENST00000307503.4	c.358+56_358+64delGGCCTCCCT		intron_variant		1	NM_000030.3	ENSP00000302620.3
AGXT	ENST00000472436.1	n.378+56_378+64delGGCCTCCCT		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44455 AN: 151678 Hom.: 7374 Cov.: 17

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.291

GnomAD3 exomes AF: 0.304 AC: 52088 AN: 171098 Hom.: 8308 AF XY: 0.311 AC XY: 28264 AN XY: 90798

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.216

Gnomad ASJ exome AF: 0.262

Gnomad EAS exome AF: 0.224

Gnomad SAS exome AF: 0.285

Gnomad FIN exome AF: 0.353

Gnomad NFE exome AF: 0.376

Gnomad OTH exome AF: 0.346

GnomAD4 exome AF: 0.363 AC: 493782 AN: 1361752 Hom.: 92247 AF XY: 0.361 AC XY: 241121 AN XY: 667088

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.229

Gnomad4 ASJ exome AF: 0.279

Gnomad4 EAS exome AF: 0.224

Gnomad4 SAS exome AF: 0.301

Gnomad4 FIN exome AF: 0.386

Gnomad4 NFE exome AF: 0.385

Gnomad4 OTH exome AF: 0.339

GnomAD4 genome AF: 0.293 AC: 44449 AN: 151796 Hom.: 7370 Cov.: 17 AF XY: 0.290 AC XY: 21527 AN XY: 74198

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.290

Alfa AF: 0.336 Hom.: 1235

Bravo AF: 0.279

Asia WGS AF: 0.270 AC: 942 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary hyperoxaluria, type I Uncertain:1

Uncertain significance, no assertion criteria provided

research

Clinical Biochemistry Laboratory, Health Services Laboratory

Nov 27, 2014

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs180177209; hg19: chr2-241808825;