rs147828466
Positions:
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_144639.3(UROC1):c.40C>T(p.Arg14Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 1,599,882 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.00095 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0016 ( 2 hom. )
Consequence
UROC1
NM_144639.3 missense
NM_144639.3 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: -0.105
Genes affected
UROC1 (HGNC:26444): (urocanate hydratase 1) This gene encodes an enzyme involved in the second step of histidine catabolism, metabolizing urocanic acid to formiminoglutamic acid. Deficiency of this enzyme results in urocanic aciduria, and is an apparent cause of mental retardation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2021]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.012254477).
BS2
?
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UROC1 | NM_144639.3 | c.40C>T | p.Arg14Trp | missense_variant | 1/20 | ENST00000290868.7 | |
UROC1 | NM_001165974.2 | c.40C>T | p.Arg14Trp | missense_variant | 1/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UROC1 | ENST00000290868.7 | c.40C>T | p.Arg14Trp | missense_variant | 1/20 | 1 | NM_144639.3 | P1 | |
UROC1 | ENST00000383579.3 | c.40C>T | p.Arg14Trp | missense_variant | 1/21 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000953 AC: 145AN: 152208Hom.: 0 Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.00105 AC: 231AN: 219108Hom.: 1 AF XY: 0.00110 AC XY: 131AN XY: 119380
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GnomAD4 exome AF: 0.00163 AC: 2353AN: 1447556Hom.: 2 Cov.: 32 AF XY: 0.00163 AC XY: 1170AN XY: 719070
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GnomAD4 genome ? AF: 0.000952 AC: 145AN: 152326Hom.: 0 Cov.: 33 AF XY: 0.000806 AC XY: 60AN XY: 74474
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ExAC
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 04, 2014 | - - |
Urocanate hydratase deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Benign
D;D
Sift4G
Uncertain
D;D
Polyphen
B;.
Vest4
MVP
MPC
0.16
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