rs180177277

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_000030.3(AGXT):​c.837T>G​(p.Ile279Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 34)

Consequence

AGXT
NM_000030.3 missense

Scores

2
7
10

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: -6.10
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.994

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AGXTNM_000030.3 linkuse as main transcriptc.837T>G p.Ile279Met missense_variant 8/11 ENST00000307503.4 NP_000021.1 P21549

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AGXTENST00000307503.4 linkuse as main transcriptc.837T>G p.Ile279Met missense_variant 8/111 NM_000030.3 ENSP00000302620.3 P21549
AGXTENST00000476698.1 linkuse as main transcriptn.489T>G non_coding_transcript_exon_variant 4/45

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
35
GnomAD4 genome
Cov.:
34

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Primary hyperoxaluria, type I Uncertain:1
Uncertain significance, no assertion criteria providedresearchClinical Biochemistry Laboratory, Health Services LaboratoryNov 27, 2014- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.085
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.030
CADD
Benign
0.027
DANN
Benign
0.95
DEOGEN2
Uncertain
0.43
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.0064
N
LIST_S2
Benign
0.80
T
M_CAP
Uncertain
0.25
D
MetaRNN
Pathogenic
0.99
D
MetaSVM
Uncertain
-0.23
T
MutationAssessor
Benign
1.5
L
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.99
N
REVEL
Uncertain
0.54
Sift
Uncertain
0.0060
D
Sift4G
Uncertain
0.013
D
Polyphen
0.60
P
Vest4
0.65
MutPred
0.88
Loss of catalytic residue at L284 (P = 0.0293);
MVP
0.37
MPC
0.046
ClinPred
0.35
T
GERP RS
-9.8
Varity_R
0.32
gMVP
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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.

Other links and lift over

dbSNP: rs180177277; hg19: chr2-241815412; API