rs58120546

chr2-240869074-T-A

Variant summary

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

The NM_000030.3(AGXT):c.165+44T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,385,060 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.00034 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0010 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: AGXT NM_000030.3 intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.0150

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGXT	NM_000030.3	c.165+44T>A		intron_variant		ENST00000307503.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGXT	ENST00000307503.4	c.165+44T>A		intron_variant		1	NM_000030.3	P1
AGXT	ENST00000472436.1	n.185+44T>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.000341 AC: 51 AN: 149574 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000367

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000332

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00106

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000374

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00102 AC: 1412 AN: 1385060 Hom.: 1 Cov.: 31 AF XY: 0.00103 AC XY: 713 AN XY: 691450

Gnomad4 AFR exome AF: 0.000943

Gnomad4 AMR exome AF: 0.000294

Gnomad4 ASJ exome AF: 0.00111

Gnomad4 EAS exome AF: 0.000303

Gnomad4 SAS exome AF: 0.000695

Gnomad4 FIN exome AF: 0.00391

Gnomad4 NFE exome AF: 0.000995

Gnomad4 OTH exome AF: 0.000585

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000341 AC: 51 AN: 149574 Hom.: 0 Cov.: 31 AF XY: 0.000398 AC XY: 29 AN XY: 72874

Gnomad4 AFR AF: 0.000367

Gnomad4 AMR AF: 0.000332

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00106

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000374

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0816 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	5.9
Dann	Benign	0.68

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: rs58120546; hg19: chr2-241808491; COSMIC: COSV56754032; COSMIC: COSV56754032;