rs1135401743
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_012205.3(HAAO):c.558G>T(p.Trp186Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
HAAO
NM_012205.3 missense
NM_012205.3 missense
Scores
7
7
5
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 4.03
Genes affected
HAAO (HGNC:4796): (3-hydroxyanthranilate 3,4-dioxygenase) 3-Hydroxyanthranilate 3,4-dioxygenase is a monomeric cytosolic protein belonging to the family of intramolecular dioxygenases containing nonheme ferrous iron. It is widely distributed in peripheral organs, such as liver and kidney, and is also present in low amounts in the central nervous system. HAAO catalyzes the synthesis of quinolinic acid (QUIN) from 3-hydroxyanthranilic acid. QUIN is an excitotoxin whose toxicity is mediated by its ability to activate glutamate N-methyl-D-aspartate receptors. Increased cerebral levels of QUIN may participate in the pathogenesis of neurologic and inflammatory disorders. HAAO has been suggested to play a role in disorders associated with altered tissue levels of QUIN. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.849
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HAAO | NM_012205.3 | c.558G>T | p.Trp186Cys | missense_variant | 7/10 | ENST00000294973.11 | |
HAAO | XM_011532729.4 | c.468G>T | p.Trp156Cys | missense_variant | 6/9 | ||
HAAO | XM_011532730.4 | c.456G>T | p.Trp152Cys | missense_variant | 8/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HAAO | ENST00000294973.11 | c.558G>T | p.Trp186Cys | missense_variant | 7/10 | 1 | NM_012205.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251050Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135690
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461698Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 727140
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GnomAD4 genome ? Cov.: 32
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32
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ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;.
Polyphen
D;.
Vest4
MutPred
Gain of catalytic residue at L187 (P = 0.0081);.;
MVP
MPC
ClinPred
D
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