chr1-39844131-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_017646.6(TRIT1):c.1204C>T(p.Arg402*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000682 in 1,613,908 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_017646.6 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TRIT1 | ENST00000316891.10 | c.1204C>T | p.Arg402* | stop_gained | Exon 10 of 11 | 1 | NM_017646.6 | ENSP00000321810.5 | ||
TRIT1 | ENST00000372818.5 | c.1126C>T | p.Arg376* | stop_gained | Exon 9 of 10 | 1 | ENSP00000361905.1 | |||
TRIT1 | ENST00000462797.5 | n.*44C>T | non_coding_transcript_exon_variant | Exon 9 of 10 | 5 | ENSP00000473773.1 | ||||
TRIT1 | ENST00000462797.5 | n.*44C>T | 3_prime_UTR_variant | Exon 9 of 10 | 5 | ENSP00000473773.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152114Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251412Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135878
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461676Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727154
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152232Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74422
ClinVar
Submissions by phenotype
Combined oxidative phosphorylation deficiency 35 Pathogenic:2Uncertain:1
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This variant is interpreted as Uncertain Significance - Insufficient Evidence, for Combined oxidative phosphorylation deficiency 35, autosomal recessive. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PVS1-Moderate => PVS1 downgraded in strength to Moderate. -
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not provided Uncertain:1
Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Nonsense variant predicted to result in protein truncation, although loss-of-function variants have not been reported downstream of this position in the protein; This variant is associated with the following publications: (PMID: 28185376) -
TRIT1 Deficiency Uncertain:1
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