2-240868842-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000030.3(AGXT):c.-24C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000377 in 1,603,376 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00056 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00036 (5 hom.)
• Consequence: AGXT NM_000030.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.175

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-240868842-C-G is Benign according to our data. Variant chr2-240868842-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 895171.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000558 (85/152354) while in subpopulation EAS AF= 0.0151 (78/5172). AF 95% confidence interval is 0.0124. There are 1 homozygotes in gnomad4. There are 50 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGXT	NM_000030.3	c.-24C>G		5_prime_UTR_variant	1/11	ENST00000307503.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGXT	ENST00000307503.4	c.-24C>G		5_prime_UTR_variant	1/11	1	NM_000030.3	P1
AGXT	ENST00000472436.1			upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.000558 AC: 85 AN: 152236 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0150

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00126 AC: 288 AN: 227934 Hom.: 2 AF XY: 0.00108 AC XY: 135 AN XY: 124500

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000304

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0159

Gnomad SAS exome AF: 0.000277

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000200

Gnomad OTH exome AF: 0.000531

GnomAD4 exome AF: 0.000358 AC: 520 AN: 1451022 Hom.: 5 Cov.: 30 AF XY: 0.000345 AC XY: 249 AN XY: 721068

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0118

Gnomad4 SAS exome AF: 0.000177

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000903

Gnomad4 OTH exome AF: 0.000517

GnomAD4 genome AF: 0.000558 AC: 85 AN: 152354 Hom.: 1 Cov.: 33 AF XY: 0.000671 AC XY: 50 AN XY: 74498

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0151

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000427 Hom.: 0

Bravo AF: 0.000688

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary hyperoxaluria, type I Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.0
Dann	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs192950967; hg19: chr2-241808259;