14-88824715-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_144596.4(TTC8):c.8C>T(p.Ser3Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,455,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S3W) has been classified as Uncertain significance.
Frequency
Consequence
NM_144596.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTC8 | NM_144596.4 | c.8C>T | p.Ser3Leu | missense_variant | 1/15 | ENST00000380656.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTC8 | ENST00000380656.7 | c.8C>T | p.Ser3Leu | missense_variant | 1/15 | 2 | NM_144596.4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000425 AC: 1AN: 235514Hom.: 0 AF XY: 0.00000777 AC XY: 1AN XY: 128730
GnomAD4 exome AF: 0.00000275 AC: 4AN: 1455674Hom.: 0 Cov.: 31 AF XY: 0.00000553 AC XY: 4AN XY: 723628
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Bardet-Biedl syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 04, 2021 | This variant is present in population databases (rs752229926, ExAC 0.003%). This sequence change replaces serine with leucine at codon 3 of the TTC8 protein (p.Ser3Leu). The serine residue is weakly conserved and there is a large physicochemical difference between serine and leucine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at