2-240871540-C-T

Variant names:

• chr2-240871540-C-T
• rs10196315
• NM_000030.3:c.524+91C>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.524+91C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 1,203,100 control chromosomes in the GnomAD database, including 77,793 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (7523 hom., cov: 33)
  • Exomes 𝑓: 0.36 (70270 hom.)
• Consequence: AGXT NM_000030.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:3
• Conservation: PhyloP100: -0.601
• Publications: 4 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 2-240871540-C-T is Benign according to our data. Variant chr2-240871540-C-T is described in ClinVar as Benign. ClinVar VariationId is 204041.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.382 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGXT	NM_000030.3	MANE Select	c.524+91C>T		intron	N/A	NP_000021.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGXT	ENST00000307503.4	TSL:1 MANE Select	c.524+91C>T		intron	N/A	ENSP00000302620.3
	AGXT	ENST00000472436.1	TSL:2	n.544+91C>T		intron	N/A
	AGXT	ENST00000476698.1	TSL:5	n.261+91C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44875 AN: 152022 Hom.: 7526 Cov.: 33

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.290

GnomAD4 exome AF: 0.359 AC: 377755 AN: 1050958 Hom.: 70270 AF XY: 0.359 AC XY: 190561 AN XY: 530940

African (AFR) AF: 0.137 AC: 3414 AN: 24936

American (AMR) AF: 0.243 AC: 8539 AN: 35118

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 6488 AN: 22924

East Asian (EAS) AF: 0.225 AC: 7642 AN: 34026

South Asian (SAS) AF: 0.306 AC: 22167 AN: 72412

European-Finnish (FIN) AF: 0.391 AC: 14792 AN: 37850

Middle Eastern (MID) AF: 0.296 AC: 1157 AN: 3906

European-Non Finnish (NFE) AF: 0.385 AC: 297825 AN: 773176

Other (OTH) AF: 0.338 AC: 15731 AN: 46610

GnomAD4 genome AF: 0.295 AC: 44871 AN: 152142 Hom.: 7523 Cov.: 33 AF XY: 0.292 AC XY: 21736 AN XY: 74368

African (AFR) AF: 0.141 AC: 5868 AN: 41514

American (AMR) AF: 0.257 AC: 3927 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 957 AN: 3468

East Asian (EAS) AF: 0.241 AC: 1245 AN: 5174

South Asian (SAS) AF: 0.281 AC: 1357 AN: 4828

European-Finnish (FIN) AF: 0.396 AC: 4196 AN: 10596

Middle Eastern (MID) AF: 0.312 AC: 91 AN: 292

European-Non Finnish (NFE) AF: 0.386 AC: 26223 AN: 67962

Other (OTH) AF: 0.289 AC: 609 AN: 2108

Alfa AF: 0.337 Hom.: 1182

Bravo AF: 0.281

Asia WGS AF: 0.270 AC: 943 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)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
DANN	Benign	0.62
PhyloP100		-0.60
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: rs10196315; hg19: chr2-241810957;