chr17-15999849-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP5
The NM_017775.4(TTC19):āc.1A>Gā(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000447 in 1,521,030 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_017775.4 start_lost
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTC19 | NM_017775.4 | c.1A>G | p.Met1? | start_lost | Exon 1 of 10 | ENST00000261647.10 | NP_060245.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152096Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000169 AC: 2AN: 118526Hom.: 0 AF XY: 0.0000151 AC XY: 1AN XY: 66086
GnomAD4 exome AF: 0.0000489 AC: 67AN: 1368934Hom.: 0 Cov.: 31 AF XY: 0.0000400 AC XY: 27AN XY: 675506
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152096Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74308
ClinVar
Submissions by phenotype
not provided Pathogenic:1Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center | Aug 18, 2020 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Mar 30, 2017 | The c.1 A>G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.1 A>G variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant alters the initiator Methionine codon, and the resultant protein would be described as p.Met1?" using a question mark to signify that it is not known if the loss of Met1 means that all protein translation is completely prevented or if an abnormal protein is produced using an alternate Met. Other loss of function variants in TTC19 have previously been reported in association with mitochondrial complex III deficiency (Stenson et al., 2014). In summary, we interpret c.1 A>G to be a likely pathogenic variant." - |
Inborn genetic diseases Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 18, 2017 | - - |
Mitochondrial complex III deficiency nuclear type 2 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Mendelics | May 04, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at