15-39582190-CAG-C
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP3
The ENST00000260356.6(THBS1):c.68-2_68-1delAG variant causes a splice acceptor, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Consequence
ENST00000260356.6 splice_acceptor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
THBS1 | NM_003246.4 | c.68_69delAG | p.Glu23fs | frameshift_variant, splice_region_variant | Exon 3 of 22 | ENST00000260356.6 | NP_003237.2 | |
THBS1 | XM_047432980.1 | c.68_69delAG | p.Glu23fs | frameshift_variant, splice_region_variant | Exon 3 of 22 | XP_047288936.1 | ||
THBS1 | XM_011521971.3 | c.68_69delAG | p.Glu23fs | frameshift_variant, splice_region_variant | Exon 3 of 21 | XP_011520273.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
THBS1 | ENST00000260356.6 | c.68-2_68-1delAG | splice_acceptor_variant, intron_variant | Intron 2 of 21 | 1 | NM_003246.4 | ENSP00000260356.5 | |||
THBS1 | ENST00000397591.2 | c.68-2_68-1delAG | splice_acceptor_variant, intron_variant | Intron 2 of 2 | 2 | ENSP00000380720.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
THBS1-related disorder Uncertain:1
The THBS1 c.68_69delAG variant is predicted to result in a frameshift and premature protein termination (p.Glu23Valfs*9). To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant 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