chr2-240869408-AGGCCTCCCT-A

Variant names:

• chr2-240869408-AGGCCTCCCT-A
• rs180177209
• NM_000030.3:c.358+56_358+64delGGCCTCCCT

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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

ENSG00000297735 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
AGXT	NM_000030.3	c.358+56_358+64delGGCCTCCCT		intron_variant	Intron 2 of 10	ENST00000307503.4	NP_000021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGXT	ENST00000307503.4	c.358+47_358+55delGGCCTCCCT		intron_variant	Intron 2 of 10	1	NM_000030.3	ENSP00000302620.3

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

GnomAD2 exomes AF: 0.304 AC: 52088 AN: 171098 AF XY: 0.311

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 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

African (AFR) AF: 0.127 AC: 3920 AN: 30836

American (AMR) AF: 0.229 AC: 7613 AN: 33184

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 5702 AN: 20464

East Asian (EAS) AF: 0.224 AC: 8718 AN: 38876

South Asian (SAS) AF: 0.301 AC: 21521 AN: 71560

European-Finnish (FIN) AF: 0.386 AC: 17699 AN: 45836

Middle Eastern (MID) AF: 0.290 AC: 1192 AN: 4108

European-Non Finnish (NFE) AF: 0.385 AC: 408387 AN: 1060788

Other (OTH) AF: 0.339 AC: 19030 AN: 56100

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

African (AFR) AF: 0.137 AC: 5701 AN: 41500

American (AMR) AF: 0.256 AC: 3917 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 950 AN: 3462

East Asian (EAS) AF: 0.238 AC: 1222 AN: 5134

South Asian (SAS) AF: 0.281 AC: 1351 AN: 4810

European-Finnish (FIN) AF: 0.395 AC: 4163 AN: 10550

Middle Eastern (MID) AF: 0.303 AC: 88 AN: 290

European-Non Finnish (NFE) AF: 0.385 AC: 26059 AN: 67768

Other (OTH) AF: 0.290 AC: 611 AN: 2110

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

Nov 27, 2014

Clinical Biochemistry Laboratory, Health Services Laboratory

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

- -

not provided Benign:1

Sep 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs180177209; hg19: chr2-241808825;