5-893096-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004237.4(TRIP13):c.92+6C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000461 in 1,583,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_004237.4 splice_region, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRIP13 | NM_004237.4 | c.92+6C>G | splice_region_variant, intron_variant | Intron 1 of 12 | ENST00000166345.8 | NP_004228.1 | ||
TRIP13 | NM_001166260.2 | c.92+6C>G | splice_region_variant, intron_variant | Intron 1 of 8 | NP_001159732.1 | |||
TRIP13 | XM_011514163.2 | c.92+6C>G | splice_region_variant, intron_variant | Intron 1 of 13 | XP_011512465.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TRIP13 | ENST00000166345.8 | c.92+6C>G | splice_region_variant, intron_variant | Intron 1 of 12 | 1 | NM_004237.4 | ENSP00000166345.3 | |||
TRIP13 | ENST00000512024.5 | n.207+6C>G | splice_region_variant, intron_variant | Intron 1 of 8 | 1 | |||||
TRIP13 | ENST00000508456.1 | n.66+6C>G | splice_region_variant, intron_variant | Intron 1 of 2 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152096Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000103 AC: 2AN: 194928Hom.: 0 AF XY: 0.00000935 AC XY: 1AN XY: 106960
GnomAD4 exome AF: 0.0000489 AC: 70AN: 1430954Hom.: 0 Cov.: 31 AF XY: 0.0000521 AC XY: 37AN XY: 710188
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152096Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74292
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change falls in intron 1 of the TRIP13 gene. It does not directly change the encoded amino acid sequence of the TRIP13 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with TRIP13-related conditions. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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. -
TRIP13-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at