rs199622789
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_017646.6(TRIT1):c.848T>G(p.Ile283Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000997 in 1,614,066 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I283V) has been classified as Uncertain significance.
Frequency
Consequence
NM_017646.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRIT1 | NM_017646.6 | c.848T>G | p.Ile283Ser | missense_variant | 7/11 | ENST00000316891.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRIT1 | ENST00000316891.10 | c.848T>G | p.Ile283Ser | missense_variant | 7/11 | 1 | NM_017646.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251374Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135850
GnomAD4 exome AF: 0.000106 AC: 155AN: 1461886Hom.: 0 Cov.: 31 AF XY: 0.000103 AC XY: 75AN XY: 727242
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74350
ClinVar
Submissions by phenotype
Combined oxidative phosphorylation deficiency 35 Pathogenic:1Uncertain:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 16, 2018 | - - |
Uncertain significance, criteria provided, single submitter | curation | SIB Swiss Institute of Bioinformatics | Oct 15, 2018 | This variant is interpreted as Uncertain Significance - Insufficient Evidence, for Combined oxidative phosphorylation deficiency 35, autosomal recessive. The following ACMG Tag(s) were applied: PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Aug 27, 2023 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 35418828, 28185376, 36047296) - |
TRIT1 Deficiency Uncertain:1
Uncertain significance, no assertion criteria provided | research | Care4Rare-SOLVE, CHEO | - | This variant was seen in a heterozygous state with c.1256A>C. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at