rs57017537

Positions:

• chr2-240869070-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_000030.3(AGXT):​c.165+40A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000385 in 106,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00076 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: AGXT NM_000030.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1 B:3
• Conservation: PhyloP100: -1.35

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-240869070-A-C is Benign according to our data. Variant chr2-240869070-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 204026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGXT	NM_000030.3	c.165+40A>C		intron_variant		ENST00000307503.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGXT	ENST00000307503.4	c.165+40A>C		intron_variant		1	NM_000030.3	P1
AGXT	ENST00000472436.1	n.185+40A>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.000385 AC: 41 AN: 106446 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000383

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000499

Gnomad OTH AF: 0.000703

GnomAD3 exomes AF: 0.00464 AC: 825 AN: 177854 Hom.: 0 AF XY: 0.00374 AC XY: 358 AN XY: 95844

Gnomad AFR exome AF: 0.00972

Gnomad AMR exome AF: 0.000762

Gnomad ASJ exome AF: 0.00586

Gnomad EAS exome AF: 0.00104

Gnomad SAS exome AF: 0.00249

Gnomad FIN exome AF: 0.0145

Gnomad NFE exome AF: 0.00502

Gnomad OTH exome AF: 0.00404

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000764 AC: 1073 AN: 1404558 Hom.: 1 Cov.: 32 AF XY: 0.000797 AC XY: 558 AN XY: 700052

Gnomad4 AFR exome AF: 0.000793

Gnomad4 AMR exome AF: 0.000249

Gnomad4 ASJ exome AF: 0.000751

Gnomad4 EAS exome AF: 0.000304

Gnomad4 SAS exome AF: 0.000520

Gnomad4 FIN exome AF: 0.00322

Gnomad4 NFE exome AF: 0.000727

Gnomad4 OTH exome AF: 0.000444

GnomAD4 genome AF: 0.000385 AC: 41 AN: 106446 Hom.: 0 Cov.: 30 AF XY: 0.000440 AC XY: 23 AN XY: 52216

Gnomad4 AFR AF: 0.000383

Gnomad4 AMR AF: 0.000170

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00103

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000499

Gnomad4 OTH AF: 0.000703

Alfa AF: 0.0760 Hom.: 0

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1 Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary hyperoxaluria, type I Uncertain:1 Benign:1

Uncertain significance, no assertion criteria provided	research	Clinical Biochemistry Laboratory, Health Services Laboratory	Nov 27, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Counsyl	Mar 23, 2017	- -

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 15, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.6
DANN	Benign	0.65

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: rs57017537; hg19: chr2-241808487; COSMIC: COSV56755570; COSMIC: COSV56755570;