5-893096-C-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_004237.4(TRIP13):c.92+6C>G variant causes a splice donor 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. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000049 ( 0 hom. )
Consequence
TRIP13
NM_004237.4 splice_donor_region, intron
NM_004237.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.0007542
2
Clinical Significance
Conservation
PhyloP100: 0.0520
Genes affected
TRIP13 (HGNC:12307): (thyroid hormone receptor interactor 13) This gene encodes a protein that interacts with thyroid hormone receptors, also known as hormone-dependent transcription factors. The gene product interacts specifically with the ligand binding domain. This gene is one of several that may play a role in early-stage non-small cell lung cancer. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
?
Variant 5-893096-C-G is Benign according to our data. Variant chr5-893096-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2817509.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRIP13 | NM_004237.4 | c.92+6C>G | splice_donor_region_variant, intron_variant | ENST00000166345.8 | |||
TRIP13 | NM_001166260.2 | c.92+6C>G | splice_donor_region_variant, intron_variant | ||||
TRIP13 | XM_011514163.2 | c.92+6C>G | splice_donor_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRIP13 | ENST00000166345.8 | c.92+6C>G | splice_donor_region_variant, intron_variant | 1 | NM_004237.4 | P1 | |||
TRIP13 | ENST00000512024.5 | n.207+6C>G | splice_donor_region_variant, intron_variant, non_coding_transcript_variant | 1 | |||||
TRIP13 | ENST00000508456.1 | n.66+6C>G | splice_donor_region_variant, intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152096Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000103 AC: 2AN: 194928Hom.: 0 AF XY: 0.00000935 AC XY: 1AN XY: 106960
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GnomAD4 exome AF: 0.0000489 AC: 70AN: 1430954Hom.: 0 Cov.: 31 AF XY: 0.0000521 AC XY: 37AN XY: 710188
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 22, 2023 | 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
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 05, 2020 | 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
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Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at