chr14-60975197-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_020810.3(TRMT5):c.1445-3C>G variant causes a splice region, splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.00000689 in 1,595,428 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 predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_020810.3 splice_region, splice_polypyrimidine_tract, 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRMT5 | NM_020810.3 | c.1445-3C>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000261249.7 | |||
TRMT5 | NM_001350253.1 | c.1529-3C>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
TRMT5 | NM_001350254.1 | c.1526-3C>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRMT5 | ENST00000261249.7 | c.1445-3C>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_020810.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152096Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000169 AC: 4AN: 236054Hom.: 0 AF XY: 0.0000312 AC XY: 4AN XY: 128126
GnomAD4 exome AF: 0.00000624 AC: 9AN: 1443332Hom.: 0 Cov.: 30 AF XY: 0.0000125 AC XY: 9AN XY: 717800
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152096Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74300
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 12, 2022 | This sequence change falls in intron 4 of the TRMT5 gene. It does not directly change the encoded amino acid sequence of the TRMT5 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with TRMT5-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 may disrupt the consensus splice site. 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