chr5-35012953-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_031900.4(AGXT2):c.1188+1G>A variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 1,551,610 control chromosomes in the GnomAD database, including 261 homozygotes. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 20 hom., cov: 33)

Exomes 𝑓: 0.016 ( 241 hom. )

Consequence

AGXT2
NM_031900.4 splice_donor, intron

Scores

Splicing: ADA: 1.000

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 7.36

Variant links:

Genes affected

AGXT2 (HGNC:14412): (alanine--glyoxylate aminotransferase 2) The protein encoded by this gene is a class III pyridoxal-phosphate-dependent mitochondrial aminotransferase. It catalyzes the conversion of glyoxylate to glycine using L-alanine as the amino donor. It is an important regulator of methylarginines and is involved in the control of blood pressure in kidney. Polymorphisms in this gene affect methylarginine and beta-aminoisobutyrate metabolism, and are associated with carotid atherosclerosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

AGXT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 5-35012953-C-T is Benign according to our data. Variant chr5-35012953-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 402346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-35012953-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0123 (1875/152332) while in subpopulation NFE AF= 0.0164 (1119/68030). AF 95% confidence interval is 0.0156. There are 20 homozygotes in gnomad4. There are 999 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGXT2	NM_031900.4 link	c.1188+1G>A		splice_donor_variant, intron_variant	Intron 11 of 13	ENST00000231420.11	NP_114106.1	Q9BYV1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGXT2	ENST00000231420.11 link	c.1188+1G>A		splice_donor_variant, intron_variant	Intron 11 of 13	1	NM_031900.4	ENSP00000231420.6		Q9BYV1-1

Frequencies

GnomAD3 genomes

AF:

0.0123

AC:

1879

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00323

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0101

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00580

Gnomad FIN

AF:

0.0352

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0165

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.0124

AC:

1933

AN:

156400

Hom.:

AF XY:

0.0123

AC XY:

1015

AN XY:

82252

show subpopulations

Gnomad AFR exome

AF:

0.00239

Gnomad AMR exome

AF:

0.00751

Gnomad ASJ exome

AF:

0.00845

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00671

Gnomad FIN exome

AF:

0.0322

Gnomad NFE exome

AF:

0.0158

Gnomad OTH exome

AF:

0.0111

GnomAD4 exome

AF:

0.0159

AC:

22251

AN:

1399278

Hom.:

241

Cov.:

AF XY:

0.0157

AC XY:

10862

AN XY:

690156

show subpopulations

Gnomad4 AFR exome

AF:

0.00326

Gnomad4 AMR exome

AF:

0.00717

Gnomad4 ASJ exome

AF:

0.00802

Gnomad4 EAS exome

AF:

0.0000560

Gnomad4 SAS exome

AF:

0.00659

Gnomad4 FIN exome

AF:

0.0321

Gnomad4 NFE exome

AF:

0.0173

Gnomad4 OTH exome

AF:

0.0146

GnomAD4 genome

AF:

0.0123

AC:

1875

AN:

152332

Hom.:

Cov.:

AF XY:

0.0134

AC XY:

999

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00322

Gnomad4 AMR

AF:

0.0100

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00581

Gnomad4 FIN

AF:

0.0352

Gnomad4 NFE

AF:

0.0164

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.0148

Hom.:

Bravo

AF:

0.00986

TwinsUK

AF:

0.0148

AC:

ALSPAC

AF:

0.0228

AC:

ESP6500AA

AF:

0.00177

AC:

ESP6500EA

AF:

0.0141

AC:

105

ExAC

AF:

0.00596

AC:

287

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 112/11414=0.98%; Frequency in ESP (EUR): 105/7450=1.4% -

Feb 20, 2017

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

AGXT2: BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.058

BayesDel_noAF

Pathogenic

0.33

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

0.89

FATHMM_MKL

Pathogenic

0.99

GERP RS

5.4

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.93

SpliceAI score (max)

0.97

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.97

Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over