17-15999855-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP5BP4BS1_Supporting
The NM_001271420.2(TTC19):c.-452C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000818 in 1,515,046 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001271420.2 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTC19 | NM_017775.4 | c.7C>T | p.Arg3Trp | missense_variant | Exon 1 of 10 | ENST00000261647.10 | NP_060245.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152110Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000188 AC: 21AN: 111676Hom.: 0 AF XY: 0.000258 AC XY: 16AN XY: 62054
GnomAD4 exome AF: 0.0000822 AC: 112AN: 1362824Hom.: 1 Cov.: 31 AF XY: 0.000128 AC XY: 86AN XY: 671918
GnomAD4 genome AF: 0.0000788 AC: 12AN: 152222Hom.: 1 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74428
ClinVar
Submissions by phenotype
not provided Pathogenic:1Uncertain:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Nov 08, 2012 | p.Arg124Trp (CGG>TGG):c.370 C>T in exon 1 of the TTC19 gene (NM_017775.3) The R124W missense change that is likely disease-associated was identified in the TTC19 gene. It has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The amino acid change is non-conservative in that a positively charged Arginine residue is replaced by an uncharged Tryptophan residue. This change occurs at a highly conserved position in the TTC19 protein. In-silico analyses are not consistent in their predictions of whether or not R124W is damaging to the TTC19 protein. Therefore, R124W is a strong candidate for a disease-causing mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in MITONUC-MITOP panel(s). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 27, 2022 | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 215303). This variant has not been reported in the literature in individuals affected with TTC19-related conditions. This variant is present in population databases (rs756830714, gnomAD 0.1%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 3 of the TTC19 protein (p.Arg3Trp). 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. - |
Mitochondrial complex III deficiency nuclear type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre | Mar 26, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at