2-165941053-C-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_024753.5(TTC21B):c.684G>A(p.Trp228*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,644 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 (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_024753.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTC21B | NM_024753.5 | c.684G>A | p.Trp228* | stop_gained | Exon 6 of 29 | ENST00000243344.8 | NP_079029.3 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251284Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135804
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461644Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727124
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Jeune thoracic dystrophy;C0687120:Nephronophthisis Pathogenic:1
This sequence change creates a premature translational stop signal (p.Trp228*) in the TTC21B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TTC21B are known to be pathogenic (PMID: 18327258, 21068128, 21258341, 23559409, 24876116, 25492405, 27491411, 29068549). This variant is present in population databases (rs777162250, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with TTC21B-related conditions. ClinVar contains an entry for this variant (Variation ID: 216125). For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at