NM_000090.4:c.1923+1G>A
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP5
The NM_000090.4(COL3A1):c.1923+1G>A variant causes a splice donor, intron change. The variant was absent in control chromosomes in GnomAD project. 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 Pathogenic (no stars).
Frequency
Consequence
NM_000090.4 splice_donor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL3A1 | ENST00000304636.9 | c.1923+1G>A | splice_donor_variant, intron_variant | Intron 27 of 50 | 1 | NM_000090.4 | ENSP00000304408.4 | |||
COL3A1 | ENST00000450867.2 | c.1824+1G>A | splice_donor_variant, intron_variant | Intron 26 of 49 | 1 | ENSP00000415346.2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, type 4 Pathogenic:2
This null variant is detected in COL3A1 where LOF is a known mechanism of disease. Protein length changes because of this variant. The classification is based on ACMG rules, with the supporting clinical evidence rules (PVS1,PM2,PM4,PP5). For these reasons, this variant has been classified as pathogenic -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at