chr4-155907791-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_005651.4(TDO2):c.302A>G(p.His101Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000031 in 1,611,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
TDO2
NM_005651.4 missense, splice_region
NM_005651.4 missense, splice_region
Scores
1
5
12
Splicing: ADA: 0.9449
1
1
Clinical Significance
Conservation
PhyloP100: 7.14
Genes affected
TDO2 (HGNC:11708): (tryptophan 2,3-dioxygenase) This gene encodes a heme enzyme that plays a critical role in tryptophan metabolism by catalyzing the first and rate-limiting step of the kynurenine pathway. Increased activity of the encoded protein and subsequent kynurenine production may also play a role in cancer through the suppression of antitumor immune responses, and single nucleotide polymorphisms in this gene may be associated with autism. [provided by RefSeq, Feb 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.27905023).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TDO2 | NM_005651.4 | c.302A>G | p.His101Arg | missense_variant, splice_region_variant | 4/12 | ENST00000536354.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TDO2 | ENST00000536354.3 | c.302A>G | p.His101Arg | missense_variant, splice_region_variant | 4/12 | 1 | NM_005651.4 | P1 | |
TDO2 | ENST00000512584.5 | n.1972A>G | splice_region_variant, non_coding_transcript_exon_variant | 1/9 | 1 | ||||
TDO2 | ENST00000506072.5 | c.-20A>G | splice_region_variant, 5_prime_UTR_variant | 6/8 | 3 | ||||
TDO2 | ENST00000507590.5 | c.-20A>G | splice_region_variant, 5_prime_UTR_variant | 5/7 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152226Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000206 AC: 3AN: 1459148Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1AN XY: 726016
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152226Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74378
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ExAC
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 19, 2022 | The c.302A>G (p.H101R) alteration is located in exon 4 (coding exon 4) of the TDO2 gene. This alteration results from a A to G substitution at nucleotide position 302, causing the histidine (H) at amino acid position 101 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at