2-240869114-C-T

Position:

• chr2-240869114-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000030.3(AGXT):​c.166-56C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00088 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0054 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AGXT NM_000030.3 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 0.266

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGXT	NM_000030.3	c.166-56C>T		intron_variant		ENST00000307503.4	NP_000021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGXT	ENST00000307503.4	c.166-56C>T		intron_variant		1	NM_000030.3	ENSP00000302620.3
AGXT	ENST00000472436.1	n.186-56C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 94 AN: 106498 Hom.: 0 Cov.: 30 FAILED QC

Gnomad AFR AF: 0.000413

Gnomad AMI AF: 0.00195

Gnomad AMR AF: 0.000931

Gnomad ASJ AF: 0.000848

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000767

Gnomad FIN AF: 0.00205

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00114

Gnomad OTH AF: 0.000707

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00542 AC: 5704 AN: 1052898 Hom.: 0 Cov.: 31 AF XY: 0.00486 AC XY: 2569 AN XY: 528282

Gnomad4 AFR exome AF: 0.00203

Gnomad4 AMR exome AF: 0.000408

Gnomad4 ASJ exome AF: 0.00201

Gnomad4 EAS exome AF: 0.0000856

Gnomad4 SAS exome AF: 0.000645

Gnomad4 FIN exome AF: 0.00124

Gnomad4 NFE exome AF: 0.00692

Gnomad4 OTH exome AF: 0.00353

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000882 AC: 94 AN: 106582 Hom.: 0 Cov.: 30 AF XY: 0.00107 AC XY: 56 AN XY: 52436

Gnomad4 AFR AF: 0.000412

Gnomad4 AMR AF: 0.000929

Gnomad4 ASJ AF: 0.000848

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000769

Gnomad4 FIN AF: 0.00205

Gnomad4 NFE AF: 0.00114

Gnomad4 OTH AF: 0.000695

Alfa AF: 0.110 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Primary hyperoxaluria, type I Uncertain:1

Uncertain significance, no assertion criteria provided

research

Clinical Biochemistry Laboratory, Health Services Laboratory

Nov 27, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.9
DANN	Benign	0.69

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: rs114401766; hg19: chr2-241808531; COSMIC: COSV56753026; COSMIC: COSV56753026;