chr1-70421649-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001902.6(CTH):c.430G>C(p.Glu144Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000753 in 1,461,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
CTH
NM_001902.6 missense
NM_001902.6 missense
Scores
5
12
Clinical Significance
Conservation
PhyloP100: 5.33
Genes affected
CTH (HGNC:2501): (cystathionine gamma-lyase) This gene encodes a cytoplasmic enzyme in the trans-sulfuration pathway that converts cystathione derived from methionine into cysteine. Glutathione synthesis in the liver is dependent upon the availability of cysteine. Mutations in this gene cause cystathioninuria. Alternative splicing of this gene results in three transcript variants encoding different isoforms. [provided by RefSeq, Jun 2010]
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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=0.27394035).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTH | NM_001902.6 | c.430G>C | p.Glu144Gln | missense_variant | 4/12 | ENST00000370938.8 | |
CTH | NM_001190463.2 | c.334G>C | p.Glu112Gln | missense_variant | 3/11 | ||
CTH | NM_153742.5 | c.430G>C | p.Glu144Gln | missense_variant | 4/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTH | ENST00000370938.8 | c.430G>C | p.Glu144Gln | missense_variant | 4/12 | 1 | NM_001902.6 | P1 | |
CTH | ENST00000346806.2 | c.430G>C | p.Glu144Gln | missense_variant | 4/11 | 1 | |||
CTH | ENST00000411986.6 | c.334G>C | p.Glu112Gln | missense_variant | 3/11 | 2 | |||
CTH | ENST00000464926.1 | n.478G>C | non_coding_transcript_exon_variant | 3/6 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251360Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135864
GnomAD3 exomes
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GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461622Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727122
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
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32
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3
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cystathioninuria Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Uncertain
Sift
Benign
T;T;D
Sift4G
Benign
T;T;T
Polyphen
0.067, 0.14
.;B;B
Vest4
MutPred
0.61
.;Gain of ubiquitination at K141 (P = 0.1103);Gain of ubiquitination at K141 (P = 0.1103);
MVP
MPC
0.15
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at