chr2-42767918-T-C
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1
The NM_012205.3(HAAO):c.641A>G(p.Tyr214Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 1,613,784 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0023 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0025 ( 8 hom. )
Consequence
HAAO
NM_012205.3 missense
NM_012205.3 missense
Scores
1
16
Clinical Significance
Conservation
PhyloP100: 0.755
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 Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.00842163).
BP6
?
Variant 2-42767918-T-C is Benign according to our data. Variant chr2-42767918-T-C is described in ClinVar as [Benign]. Clinvar id is 3037735.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00234 (356/152348) while in subpopulation NFE AF= 0.00275 (187/68026). AF 95% confidence interval is 0.00243. There are 0 homozygotes in gnomad4. There are 184 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HAAO | NM_012205.3 | c.641A>G | p.Tyr214Cys | missense_variant | 8/10 | ENST00000294973.11 | |
HAAO | XM_011532729.4 | c.551A>G | p.Tyr184Cys | missense_variant | 7/9 | ||
HAAO | XM_011532730.4 | c.539A>G | p.Tyr180Cys | missense_variant | 9/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HAAO | ENST00000294973.11 | c.641A>G | p.Tyr214Cys | missense_variant | 8/10 | 1 | NM_012205.3 | P1 | |
HAAO | ENST00000402698.6 | n.985A>G | non_coding_transcript_exon_variant | 7/9 | 5 | ||||
HAAO | ENST00000404451.7 | n.400A>G | non_coding_transcript_exon_variant | 6/6 | 3 | ||||
HAAO | ENST00000406007.6 | n.192A>G | non_coding_transcript_exon_variant | 2/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00235 AC: 358AN: 152230Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.00252 AC: 632AN: 251112Hom.: 1 AF XY: 0.00256 AC XY: 347AN XY: 135712
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GnomAD4 exome AF: 0.00250 AC: 3660AN: 1461436Hom.: 8 Cov.: 31 AF XY: 0.00239 AC XY: 1741AN XY: 727052
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
HAAO-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 17, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
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