rs57017537

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_000030.3(AGXT):c.165+40A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000385 in 106,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00076 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

AGXT
NM_000030.3 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts U:1B:3

Conservation

PhyloP100: -1.35

Publications

3 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: G2P, Myriad Women’s Health, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

AGXT links:

ENSG00000297735 (HGNC:):

ENSG00000297735 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 2-240869070-A-C is Benign according to our data. Variant chr2-240869070-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 204026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGXT	NM_000030.3 link	c.165+40A>C		intron_variant	Intron 1 of 10	ENST00000307503.4	NP_000021.1	P21549

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGXT	ENST00000307503.4 link	c.165+40A>C		intron_variant	Intron 1 of 10	1	NM_000030.3	ENSP00000302620.3		P21549

Frequencies

GnomAD3 genomes

AF:

0.000385

AC:

AN:

106446

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000383

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000499

Gnomad OTH

AF:

0.000703

GnomAD2 exomes

AF:

0.00464

AC:

825

AN:

177854

AF XY:

0.00374

show subpopulations

Gnomad AFR exome

AF:

0.00972

Gnomad AMR exome

AF:

0.000762

Gnomad ASJ exome

AF:

0.00586

Gnomad EAS exome

AF:

0.00104

Gnomad FIN exome

AF:

0.0145

Gnomad NFE exome

AF:

0.00502

Gnomad OTH exome

AF:

0.00404

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000764

AC:

1073

AN:

1404558

Hom.:

Cov.:

AF XY:

0.000797

AC XY:

558

AN XY:

700052

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000793

AC:

AN:

32776

American (AMR)

AF:

0.000249

AC:

AN:

44180

Ashkenazi Jewish (ASJ)

AF:

0.000751

AC:

AN:

25316

East Asian (EAS)

AF:

0.000304

AC:

AN:

39482

South Asian (SAS)

AF:

0.000520

AC:

AN:

84608

European-Finnish (FIN)

AF:

0.00322

AC:

159

AN:

49354

Middle Eastern (MID)

AF:

0.000354

AC:

AN:

5644

European-Non Finnish (NFE)

AF:

0.000727

AC:

774

AN:

1064696

Other (OTH)

AF:

0.000444

AC:

AN:

58502

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.286

Heterozygous variant carriers

105

210

316

421

526

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

104

130

<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:

0.000385

AC:

AN:

106446

Hom.:

Cov.:

AF XY:

0.000440

AC XY:

AN XY:

52216

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000383

AC:

AN:

31372

American (AMR)

AF:

0.000170

AC:

AN:

11792

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2366

East Asian (EAS)

AF:

0.00

AC:

AN:

4456

South Asian (SAS)

AF:

0.00103

AC:

AN:

3902

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6350

Middle Eastern (MID)

AF:

0.00

AC:

AN:

198

European-Non Finnish (NFE)

AF:

0.000499

AC:

AN:

44072

Other (OTH)

AF:

0.000703

AC:

AN:

1422

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.268

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0760

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary hyperoxaluria, type I

Uncertain:1Benign:1

Mar 23, 2017

Counsyl

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. -

Nov 27, 2014

Clinical Biochemistry Laboratory, Health Services Laboratory

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:research

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 15, 2019

GeneDx

Significance:Likely 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

-0.91

CADD

Benign

3.6

(source)

DANN

Benign

0.65

PhyloP100

-1.3

PromoterAI

0.011

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over