15-43233553-C-T
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_201631.4(TGM5):c.2009+1G>A variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.0000458 in 1,614,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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_201631.4 splice_donor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TGM5 | NM_201631.4 | c.2009+1G>A | splice_donor_variant, intron_variant | Intron 12 of 12 | ENST00000220420.10 | NP_963925.2 | ||
TGM5 | NM_004245.4 | c.1763+1G>A | splice_donor_variant, intron_variant | Intron 11 of 11 | NP_004236.1 | |||
TGM5 | XM_011522230.3 | c.980+1G>A | splice_donor_variant, intron_variant | Intron 6 of 6 | XP_011520532.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TGM5 | ENST00000220420.10 | c.2009+1G>A | splice_donor_variant, intron_variant | Intron 12 of 12 | 1 | NM_201631.4 | ENSP00000220420.5 | |||
TGM5 | ENST00000349114.8 | c.1763+1G>A | splice_donor_variant, intron_variant | Intron 11 of 11 | 1 | ENSP00000220419.8 | ||||
TGM5 | ENST00000396996.3 | n.1485+1G>A | splice_donor_variant, intron_variant | Intron 5 of 5 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152200Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251476Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135914
GnomAD4 exome AF: 0.0000465 AC: 68AN: 1461870Hom.: 0 Cov.: 31 AF XY: 0.0000550 AC XY: 40AN XY: 727238
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74344
ClinVar
Submissions by phenotype
not provided Uncertain:1
Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at