15-43233581-C-CAG
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_201631.4(TGM5):c.1981_1982insCT(p.Gly661AlafsTer41) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000248 in 1,614,058 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Consequence
NM_201631.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TGM5 | NM_201631.4 | c.1981_1982insCT | p.Gly661AlafsTer41 | frameshift_variant | Exon 12 of 13 | ENST00000220420.10 | NP_963925.2 | |
TGM5 | NM_004245.4 | c.1735_1736insCT | p.Gly579AlafsTer41 | frameshift_variant | Exon 11 of 12 | NP_004236.1 | ||
TGM5 | XM_011522230.3 | c.952_953insCT | p.Gly318AlafsTer41 | frameshift_variant | Exon 6 of 7 | XP_011520532.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TGM5 | ENST00000220420.10 | c.1981_1982insCT | p.Gly661AlafsTer41 | frameshift_variant | Exon 12 of 13 | 1 | NM_201631.4 | ENSP00000220420.5 | ||
TGM5 | ENST00000349114.8 | c.1735_1736insCT | p.Gly579AlafsTer41 | frameshift_variant | Exon 11 of 12 | 1 | ENSP00000220419.8 | |||
TGM5 | ENST00000396996.3 | n.1457_1458insCT | non_coding_transcript_exon_variant | Exon 5 of 6 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152172Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251484Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135914
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461886Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727242
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74344
ClinVar
Submissions by phenotype
TGM5-related disorder Uncertain:1
The TGM5 c.1981_1982insCT variant is predicted to result in a frameshift and premature protein termination (p.Gly661Alafs*41). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0018% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant resides in the penultimate exon and the gene product may escape nonsense mediated decay. No other loss-of-function variants have been reported in association with disease downstream of this variant (Human Gene Mutation Database, http://www.hgmd.cf.ac.uk/ac/index.php). Although we suspect that this variant may be pathogenic, at this time the clinical significance is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at