NM_000030.3:c.680+17C>T

Variant names:

• chr2-240874079-C-T
• rs11693280
• NM_000030.3:c.680+17C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000030.3(AGXT):​c.680+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,610,752 control chromosomes in the GnomAD database, including 29,411 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2026 hom., cov: 33)
  • Exomes 𝑓: 0.19 (27385 hom.)
• Consequence: AGXT NM_000030.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:4
• Conservation: PhyloP100: -1.97
• Publications: 5 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: G2P, Myriad Women’s Health, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 2-240874079-C-T is Benign according to our data. Variant chr2-240874079-C-T is described in ClinVar as Benign. ClinVar VariationId is 204043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

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.680+17C>T		intron	N/A	NP_000021.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGXT	ENST00000307503.4	TSL:1 MANE Select	c.680+17C>T		intron	N/A	ENSP00000302620.3
	AGXT	ENST00000908235.1		c.680+17C>T		intron	N/A	ENSP00000578294.1
	AGXT	ENST00000908236.1		c.680+17C>T		intron	N/A	ENSP00000578295.1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22121 AN: 152126 Hom.: 2023 Cov.: 33

Gnomad AFR AF: 0.0604

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.0732

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.159

GnomAD2 exomes AF: 0.148 AC: 36944 AN: 249928 AF XY: 0.150

Gnomad AFR exome AF: 0.0613

Gnomad AMR exome AF: 0.0809

Gnomad ASJ exome AF: 0.182

Gnomad EAS exome AF: 0.000327

Gnomad FIN exome AF: 0.245

Gnomad NFE exome AF: 0.203

Gnomad OTH exome AF: 0.169

GnomAD4 exome AF: 0.185 AC: 270108 AN: 1458508 Hom.: 27385 Cov.: 32 AF XY: 0.182 AC XY: 132203 AN XY: 725746

African (AFR) AF: 0.0609 AC: 2035 AN: 33422

American (AMR) AF: 0.0838 AC: 3745 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 4651 AN: 26108

East Asian (EAS) AF: 0.000328 AC: 13 AN: 39686

South Asian (SAS) AF: 0.0763 AC: 6577 AN: 86206

European-Finnish (FIN) AF: 0.239 AC: 12557 AN: 52562

Middle Eastern (MID) AF: 0.165 AC: 952 AN: 5764

European-Non Finnish (NFE) AF: 0.207 AC: 229399 AN: 1109780

Other (OTH) AF: 0.169 AC: 10179 AN: 60276

GnomAD4 genome AF: 0.145 AC: 22126 AN: 152244 Hom.: 2026 Cov.: 33 AF XY: 0.144 AC XY: 10700 AN XY: 74440

African (AFR) AF: 0.0604 AC: 2511 AN: 41562

American (AMR) AF: 0.119 AC: 1827 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 620 AN: 3470

East Asian (EAS) AF: 0.000967 AC: 5 AN: 5168

South Asian (SAS) AF: 0.0741 AC: 357 AN: 4820

European-Finnish (FIN) AF: 0.236 AC: 2504 AN: 10596

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13683 AN: 67994

Other (OTH) AF: 0.157 AC: 332 AN: 2116

Alfa AF: 0.128 Hom.: 315

Bravo AF: 0.135

Asia WGS AF: 0.0340 AC: 117 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.1
DANN	Benign	0.88
PhyloP100		-2.0
Mutation Taster		=100/0	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: rs11693280; hg19: chr2-241813496; COSMIC: COSV56755721; COSMIC: COSV56755721;