rs66494441

Variant names:

• chr2-240869046-A-G
• rs66494441
• NM_000030.3:c.165+16A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-240869046-A-G
• chr2-240869046-A-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.165+16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,609,108 control chromosomes in the GnomAD database, including 30,255 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2351 hom., cov: 33)
  • Exomes 𝑓: 0.19 (27904 hom.)
• Consequence: AGXT NM_000030.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:5
• Conservation: PhyloP100: -2.42
• Publications: 7 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

ENSG00000297735 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-240869046-A-G is Benign according to our data. Variant chr2-240869046-A-G is described in ClinVar as Benign. ClinVar VariationId is 204021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGXT	NM_000030.3	c.165+16A>G		intron_variant	Intron 1 of 10	ENST00000307503.4	NP_000021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGXT	ENST00000307503.4	c.165+16A>G		intron_variant	Intron 1 of 10	1	NM_000030.3	ENSP00000302620.3

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25708 AN: 151760 Hom.: 2341 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.0726

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.182

GnomAD2 exomes AF: 0.160 AC: 39256 AN: 244910 AF XY: 0.163

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.0878

Gnomad ASJ exome AF: 0.178

Gnomad EAS exome AF: 0.0861

Gnomad FIN exome AF: 0.234

Gnomad NFE exome AF: 0.200

Gnomad OTH exome AF: 0.172

GnomAD4 exome AF: 0.191 AC: 277793 AN: 1457230 Hom.: 27904 Cov.: 33 AF XY: 0.188 AC XY: 136241 AN XY: 724742

African (AFR) AF: 0.135 AC: 4513 AN: 33428

American (AMR) AF: 0.0906 AC: 4046 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 4619 AN: 26060

East Asian (EAS) AF: 0.0773 AC: 3064 AN: 39662

South Asian (SAS) AF: 0.104 AC: 8964 AN: 86144

European-Finnish (FIN) AF: 0.234 AC: 11968 AN: 51234

Middle Eastern (MID) AF: 0.172 AC: 991 AN: 5760

European-Non Finnish (NFE) AF: 0.206 AC: 228943 AN: 1109986

Other (OTH) AF: 0.177 AC: 10685 AN: 60282

GnomAD4 genome AF: 0.169 AC: 25735 AN: 151878 Hom.: 2351 Cov.: 33 AF XY: 0.168 AC XY: 12463 AN XY: 74206

African (AFR) AF: 0.132 AC: 5488 AN: 41438

American (AMR) AF: 0.125 AC: 1905 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 619 AN: 3470

East Asian (EAS) AF: 0.0726 AC: 372 AN: 5124

South Asian (SAS) AF: 0.104 AC: 498 AN: 4792

European-Finnish (FIN) AF: 0.237 AC: 2504 AN: 10550

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13677 AN: 67916

Other (OTH) AF: 0.179 AC: 379 AN: 2112

Alfa AF: 0.124 Hom.: 260

Asia WGS AF: 0.0740 AC: 259 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1 Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Aug 07, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 26, 2017

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: The AGXT c.165+16A>G variant involves the alteration of a non-conserved intronic nucleotide at a position not widely known to affect splicing. Mutation taster predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 19192/117856 control chromosomes (1649 homozygotes) from ExAC at a frequency of 0.1628428, which is approximately 69 times the estimated maximal expected allele frequency of a pathogenic AGXT variant (0.0023717), thus this variant is a common benign polymorphism. This variant, as a part of a haplotype, has been reported in patients with primary hyperoxaluria type 1 in whom another pathogenic variant (p.Ile244Thr) in homozygosity explained the phenotype, further supporting the benign nature (Kanoun_2013). One clinical diagnostic laboratory (via ClinVar) has classified it as benign. Taken together, this variant is classified as benign. -

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Primary hyperoxaluria, type I Uncertain:1

Nov 27, 2014

Clinical Biochemistry Laboratory, Health Services Laboratory

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.90
DANN	Benign	0.44
PhyloP100		-2.4
PromoterAI		0.042	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs66494441; hg19: chr2-241808463;