2-240873037-A-C
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Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The NM_000030.3(AGXT):āc.583A>Cā(p.Met195Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
AGXT
NM_000030.3 missense
NM_000030.3 missense
Scores
5
7
7
Clinical Significance
Conservation
PhyloP100: 4.25
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 Uncertain_significance. Variant got 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.892
PP5
Variant 2-240873037-A-C is Pathogenic according to our data. Variant chr2-240873037-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 204112.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AGXT | NM_000030.3 | c.583A>C | p.Met195Leu | missense_variant | 5/11 | ENST00000307503.4 | NP_000021.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AGXT | ENST00000307503.4 | c.583A>C | p.Met195Leu | missense_variant | 5/11 | 1 | NM_000030.3 | ENSP00000302620.3 | ||
AGXT | ENST00000472436.1 | n.603A>C | non_coding_transcript_exon_variant | 5/5 | 2 | |||||
AGXT | ENST00000476698.1 | n.320A>C | non_coding_transcript_exon_variant | 2/4 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249422Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134964
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461386Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727074
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Primary hyperoxaluria, type I Pathogenic:1
Pathogenic, no assertion criteria provided | in vitro | Clinical Biochemistry Laboratory, Health Services Laboratory | Nov 27, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Benign
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Pathogenic
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Gain of catalytic residue at M195 (P = 0.0541);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at