2-142960633-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The ENST00000264170.9(KYNU):āc.592A>Gā(p.Thr198Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,461,408 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: 0.0000041 ( 0 hom. )
Consequence
KYNU
ENST00000264170.9 missense
ENST00000264170.9 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 6.50
Genes affected
KYNU (HGNC:6469): (kynureninase) Kynureninase is a pyridoxal-5'-phosphate (pyridoxal-P) dependent enzyme that catalyzes the cleavage of L-kynurenine and L-3-hydroxykynurenine into anthranilic and 3-hydroxyanthranilic acids, respectively. Kynureninase is involved in the biosynthesis of NAD cofactors from tryptophan through the kynurenine pathway. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2010]
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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, 0.868
PP5
Variant 2-142960633-A-G is Pathogenic according to our data. Variant chr2-142960633-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 160355.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-142960633-A-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KYNU | NM_003937.3 | c.592A>G | p.Thr198Ala | missense_variant | 8/14 | ENST00000264170.9 | NP_003928.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KYNU | ENST00000264170.9 | c.592A>G | p.Thr198Ala | missense_variant | 8/14 | 1 | NM_003937.3 | ENSP00000264170 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251006Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135648
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461408Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727054
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GnomAD4 genome Cov.: 32
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32
ExAC
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hydroxykynureninuria Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 01, 2007 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
DEOGEN2
Uncertain
T;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D;D;T
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;.
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;N;D;.
REVEL
Uncertain
Sift
Benign
T;T;T;.
Sift4G
Benign
T;T;T;T
Polyphen
B;.;B;.
Vest4
MutPred
Loss of phosphorylation at T198 (P = 0.0649);Loss of phosphorylation at T198 (P = 0.0649);Loss of phosphorylation at T198 (P = 0.0649);.;
MVP
MPC
ClinPred
T
GERP RS
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