2-240875890-C-T

Variant names:

• chr2-240875890-C-T
• rs12478859
• NM_000030.3:c.777-45C>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.777-45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 1,598,714 control chromosomes in the GnomAD database, including 112,089 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (8015 hom., cov: 34)
  • Exomes 𝑓: 0.37 (104074 hom.)
• Consequence: AGXT NM_000030.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:2
• Conservation: PhyloP100: -0.176
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-240875890-C-T is Benign according to our data. Variant chr2-240875890-C-T is described in ClinVar as Benign. ClinVar VariationId is 204050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGXT	NM_000030.3	c.777-45C>T		intron_variant	Intron 7 of 10	ENST00000307503.4	NP_000021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGXT	ENST00000307503.4	c.777-45C>T		intron_variant	Intron 7 of 10	1	NM_000030.3	ENSP00000302620.3
AGXT	ENST00000476698.1	n.429-45C>T		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46936 AN: 151966 Hom.: 8014 Cov.: 34

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.323

GnomAD2 exomes AF: 0.325 AC: 80376 AN: 247112 AF XY: 0.329

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.240

Gnomad ASJ exome AF: 0.345

Gnomad EAS exome AF: 0.194

Gnomad FIN exome AF: 0.447

Gnomad NFE exome AF: 0.394

Gnomad OTH exome AF: 0.348

GnomAD4 exome AF: 0.372 AC: 538410 AN: 1446630 Hom.: 104074 Cov.: 29 AF XY: 0.369 AC XY: 265947 AN XY: 720406

African (AFR) AF: 0.166 AC: 5501 AN: 33102

American (AMR) AF: 0.242 AC: 10772 AN: 44544

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 8835 AN: 26036

East Asian (EAS) AF: 0.169 AC: 6705 AN: 39566

South Asian (SAS) AF: 0.241 AC: 20697 AN: 85736

European-Finnish (FIN) AF: 0.442 AC: 23562 AN: 53272

Middle Eastern (MID) AF: 0.319 AC: 1829 AN: 5738

European-Non Finnish (NFE) AF: 0.400 AC: 439189 AN: 1098746

Other (OTH) AF: 0.356 AC: 21320 AN: 59890

GnomAD4 genome AF: 0.309 AC: 46945 AN: 152084 Hom.: 8015 Cov.: 34 AF XY: 0.308 AC XY: 22909 AN XY: 74324

African (AFR) AF: 0.168 AC: 6961 AN: 41532

American (AMR) AF: 0.268 AC: 4097 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1180 AN: 3472

East Asian (EAS) AF: 0.191 AC: 986 AN: 5164

South Asian (SAS) AF: 0.230 AC: 1110 AN: 4818

European-Finnish (FIN) AF: 0.452 AC: 4782 AN: 10568

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26786 AN: 67928

Other (OTH) AF: 0.322 AC: 679 AN: 2110

Alfa AF: 0.289 Hom.: 1227

Bravo AF: 0.292

Asia WGS AF: 0.210 AC: 730 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Aug 07, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.7
DANN	Benign	0.82
PhyloP100		-0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12478859; hg19: chr2-241815307; COSMIC: COSV56754430; COSMIC: COSV56754430;