rs786204090
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP3BS1_Supporting
The NM_144596.4(TTC8):āc.484G>Cā(p.Gly162Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,461,768 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_144596.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000997 AC: 25AN: 250742Hom.: 1 AF XY: 0.0000885 AC XY: 12AN XY: 135566
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461768Hom.: 1 Cov.: 33 AF XY: 0.0000179 AC XY: 13AN XY: 727178
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
TTC8-related disorder Uncertain:1
The TTC8 c.484G>C variant is predicted to result in the amino acid substitution p.Gly162Arg. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.072% of alleles in individuals of Latino descent in gnomAD, including 1 homozygote. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Bardet-Biedl syndrome Uncertain:1
This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 152 of the TTC8 protein (p.Gly152Arg). This variant is present in population databases (rs753150258, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with TTC8-related conditions. ClinVar contains an entry for this variant (Variation ID: 188127). Invitae Evidence 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 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. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at