chr2-240871540-C-T

Position:

• chr2-240871540-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000030.3(AGXT):​c.524+91C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 1,203,100 control chromosomes in the GnomAD database, including 77,793 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (7523 hom., cov: 33)
  • Exomes 𝑓: 0.36 (70270 hom.)
• Consequence: AGXT NM_000030.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:3
• Conservation: PhyloP100: -0.601

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-240871540-C-T is Benign according to our data. Variant chr2-240871540-C-T is described in ClinVar as [Benign]. Clinvar id is 204041.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGXT	NM_000030.3	c.524+91C>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.524+91C>T		intron_variant		1	NM_000030.3	ENSP00000302620	P1
AGXT	ENST00000472436.1	n.544+91C>T		intron_variant, non_coding_transcript_variant		2
AGXT	ENST00000476698.1	n.261+91C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44875 AN: 152022 Hom.: 7526 Cov.: 33

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.290

GnomAD4 exome AF: 0.359 AC: 377755 AN: 1050958 Hom.: 70270 AF XY: 0.359 AC XY: 190561 AN XY: 530940

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.243

Gnomad4 ASJ exome AF: 0.283

Gnomad4 EAS exome AF: 0.225

Gnomad4 SAS exome AF: 0.306

Gnomad4 FIN exome AF: 0.391

Gnomad4 NFE exome AF: 0.385

Gnomad4 OTH exome AF: 0.338

GnomAD4 genome AF: 0.295 AC: 44871 AN: 152142 Hom.: 7523 Cov.: 33 AF XY: 0.292 AC XY: 21736 AN XY: 74368

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.289

Alfa AF: 0.337 Hom.: 1182

Bravo AF: 0.281

Asia WGS AF: 0.270 AC: 943 AN: 3478

ClinVar

Significance: 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	Genome-Nilou Lab	Jul 10, 2021	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 07, 2018	- -
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	-0.82
CADD	Benign	1.6
DANN	Benign	0.62

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: rs10196315; hg19: chr2-241810957;