5-893094-A-AG
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004237.4(TRIP13):c.92+5dupG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000957 in 1,587,876 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 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
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRIP13 | NM_004237.4 | c.92+5dupG | splice_region_variant, intron_variant | Intron 1 of 12 | ENST00000166345.8 | NP_004228.1 | ||
TRIP13 | NM_001166260.2 | c.92+5dupG | splice_region_variant, intron_variant | Intron 1 of 8 | NP_001159732.1 | |||
TRIP13 | XM_011514163.2 | c.92+5dupG | 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+4_92+5insG | splice_region_variant, intron_variant | Intron 1 of 12 | 1 | NM_004237.4 | ENSP00000166345.3 | |||
TRIP13 | ENST00000512024.5 | n.207+4_207+5insG | splice_region_variant, intron_variant | Intron 1 of 8 | 1 | |||||
TRIP13 | ENST00000508456.1 | n.66+4_66+5insG | splice_region_variant, intron_variant | Intron 1 of 2 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000857 AC: 13AN: 151766Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000493 AC: 10AN: 202984Hom.: 0 AF XY: 0.0000359 AC XY: 4AN XY: 111518
GnomAD4 exome AF: 0.0000968 AC: 139AN: 1435994Hom.: 0 Cov.: 31 AF XY: 0.0000869 AC XY: 62AN XY: 713080
GnomAD4 genome AF: 0.0000856 AC: 13AN: 151882Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6AN XY: 74246
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 (rs762118615, gnomAD 0.01%). 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at