17-3656487-T-G
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_004937.3(CTNS):āc.462T>Gā(p.Ser154Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S154S) has been classified as Benign.
Frequency
Consequence
NM_004937.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CTNS | NM_004937.3 | c.462T>G | p.Ser154Arg | missense_variant, splice_region_variant | Exon 8 of 12 | ENST00000046640.9 | NP_004928.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 129606Hom.: 0 Cov.: 17 FAILED QC
GnomAD3 exomes AF: 0.00000818 AC: 2AN: 244426Hom.: 0 AF XY: 0.00000755 AC XY: 1AN XY: 132416
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1457946Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 725056
GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 129606Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0AN XY: 62010
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.462T>G (p.S154R) alteration is located in exon 8 (coding exon 6) of the CTNS gene. This alteration results from a T to G substitution at nucleotide position 462, causing the serine (S) at amino acid position 154 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at