dbSNP rs12478859: AGXT:c.777-45C>T (chr2-240875890-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:2

Conservation

PhyloP100: -0.176

Publications

7 publications found

Variant links:

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

AGXT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

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.777-45C>T		intron	N/A	NP_000021.1	P21549

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AGXT	ENST00000307503.4	TSL:1 MANE Select	c.777-45C>T	intron	N/A	ENSP00000302620.3	P21549
AGXT	ENST00000908235.1		c.777-45C>T	intron	N/A	ENSP00000578294.1
AGXT	ENST00000908236.1		c.777-45C>T	intron	N/A	ENSP00000578295.1

Frequencies

GnomAD3 genomes

AF:

0.309

AC:

46936

AN:

151966

Hom.:

8014

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.369

AC XY:

265947

AN XY:

720406

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

18217

36434

54651

72868

91085

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13352

26704

40056

53408

66760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.309

AC:

46945

AN:

152084

Hom.:

8015

Cov.:

AF XY:

0.308

AC XY:

22909

AN XY:

74324

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1702

3405

5107

6810

8512

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

468

936

1404

1872

2340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.289

Hom.:

1227

Bravo

AF:

0.292

Asia WGS

AF:

0.210

AC:

730

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Primary hyperoxaluria, type I (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.7

(source)

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)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over