chr14-88824730-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_144596.4(TTC8):c.23T>A(p.Leu8Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,610,732 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 Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. L8L) has been classified as Likely benign.
Frequency
Consequence
NM_144596.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTC8 | NM_144596.4 | c.23T>A | p.Leu8Gln | missense_variant | 1/15 | ENST00000380656.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTC8 | ENST00000380656.7 | c.23T>A | p.Leu8Gln | missense_variant | 1/15 | 2 | NM_144596.4 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152098Hom.: 0 Cov.: 32
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1458634Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 725290
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152098Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74298
ClinVar
Submissions by phenotype
Bardet-Biedl syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 15, 2022 | This variant has not been reported in the literature in individuals affected with TTC8-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TTC8 protein function. ClinVar contains an entry for this variant (Variation ID: 1471826). This variant is present in population databases (no rsID available, gnomAD 0.1%). This sequence change replaces leucine, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 8 of the TTC8 protein (p.Leu8Gln). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at