rs116057889

Variant names:

• chr2-240868843-G-A
• rs116057889
• NM_000030.3:c.-23G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-240868843-G-A
• chr2-240868843-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000030.3(AGXT):​c.-23G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00257 in 1,602,954 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (51 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (35 hom.)
• Consequence: AGXT NM_000030.3 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.00800
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• alanine glyoxylate aminotransferase deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• primary hyperoxaluria type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Orphanet, Labcorp Genetics (formerly Invitae), Myriad Women’s Health

ENSG00000297735 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 2-240868843-G-A is Benign according to our data. Variant chr2-240868843-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 335292.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0138 (2097/152302) while in subpopulation AFR AF = 0.0466 (1937/41568). AF 95% confidence interval is 0.0449. There are 51 homozygotes in GnomAd4. There are 947 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 51 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000030.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGXT	NM_000030.3	MANE Select	c.-23G>A		5_prime_UTR	Exon 1 of 11	NP_000021.1	P21549

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGXT	ENST00000307503.4	TSL:1 MANE Select	c.-23G>A		5_prime_UTR	Exon 1 of 11	ENSP00000302620.3	P21549
	AGXT	ENST00000908235.1		c.-23G>A		5_prime_UTR	Exon 1 of 12	ENSP00000578294.1
	AGXT	ENST00000908236.1		c.-23G>A		5_prime_UTR	Exon 1 of 12	ENSP00000578295.1

Frequencies

GnomAD3 genomes AF: 0.0138 AC: 2101 AN: 152184 Hom.: 52 Cov.: 33

Gnomad AFR AF: 0.0468

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00805

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00957

GnomAD2 exomes AF: 0.00374 AC: 850 AN: 227076 AF XY: 0.00263

Gnomad AFR exome AF: 0.0510

Gnomad AMR exome AF: 0.00385

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000175

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000130

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00140 AC: 2027 AN: 1450652 Hom.: 35 Cov.: 30 AF XY: 0.00116 AC XY: 839 AN XY: 720876

African (AFR) AF: 0.0468 AC: 1557 AN: 33272

American (AMR) AF: 0.00427 AC: 185 AN: 43286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25906

East Asian (EAS) AF: 0.0000511 AC: 2 AN: 39132

South Asian (SAS) AF: 0.000130 AC: 11 AN: 84774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51252

Middle Eastern (MID) AF: 0.000696 AC: 4 AN: 5750

European-Non Finnish (NFE) AF: 0.0000677 AC: 75 AN: 1107360

Other (OTH) AF: 0.00322 AC: 193 AN: 59920

GnomAD4 genome AF: 0.0138 AC: 2097 AN: 152302 Hom.: 51 Cov.: 33 AF XY: 0.0127 AC XY: 947 AN XY: 74468

African (AFR) AF: 0.0466 AC: 1937 AN: 41568

American (AMR) AF: 0.00804 AC: 123 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68014

Other (OTH) AF: 0.00947 AC: 20 AN: 2112

Alfa AF: 0.00284 Hom.: 1

Bravo AF: 0.0160

Asia WGS AF: 0.00289 AC: 11 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Primary hyperoxaluria, type I (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.59
PhyloP100		-0.0080
PromoterAI		-0.015	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs116057889; hg19: chr2-241808260;