rs28941786
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_001902.6(CTH):āc.718C>Gā(p.Gln240Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000287 in 1,393,214 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: 0.0000029 ( 0 hom. )
Consequence
CTH
NM_001902.6 missense
NM_001902.6 missense
Scores
7
9
1
Clinical Significance
Conservation
PhyloP100: 7.57
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 Likely_pathogenic. Variant got 7 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.975
PP5
?
Variant 1-70430388-C-G is Pathogenic according to our data. Variant chr1-70430388-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 2940.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTH | NM_001902.6 | c.718C>G | p.Gln240Glu | missense_variant | 7/12 | ENST00000370938.8 | |
CTH | NM_001190463.2 | c.622C>G | p.Gln208Glu | missense_variant | 6/11 | ||
CTH | NM_153742.5 | c.586C>G | p.Gln196Glu | missense_variant | 6/11 | ||
CTH | XM_017000416.3 | c.148C>G | p.Gln50Glu | missense_variant | 4/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTH | ENST00000370938.8 | c.718C>G | p.Gln240Glu | missense_variant | 7/12 | 1 | NM_001902.6 | P1 | |
CTH | ENST00000346806.2 | c.586C>G | p.Gln196Glu | missense_variant | 6/11 | 1 | |||
CTH | ENST00000411986.6 | c.622C>G | p.Gln208Glu | missense_variant | 6/11 | 2 | |||
CTH | ENST00000464926.1 | n.766C>G | non_coding_transcript_exon_variant | 6/6 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251346Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135864
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GnomAD4 exome AF: 0.00000287 AC: 4AN: 1393214Hom.: 0 Cov.: 23 AF XY: 0.00000143 AC XY: 1AN XY: 697500
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Cystathioninuria Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 01, 2003 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
A;A;A
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
1.0
.;D;D
Vest4
MutPred
0.87
.;Gain of methylation at R237 (P = 0.0747);.;
MVP
MPC
0.49
ClinPred
D
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