rs67368147
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2PM5PP2PP3_StrongPP5
The NM_000088.4(COL1A1):c.2110G>T(p.Gly704Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 11/19 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G704S) has been classified as Pathogenic.
Frequency
Consequence
NM_000088.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL1A1 | NM_000088.4 | c.2110G>T | p.Gly704Cys | missense_variant | 31/51 | ENST00000225964.10 | |
COL1A1 | XM_011524341.2 | c.1912G>T | p.Gly638Cys | missense_variant | 28/48 | ||
COL1A1 | XM_005257058.5 | c.2110G>T | p.Gly704Cys | missense_variant | 31/49 | ||
COL1A1 | XM_005257059.5 | c.1192G>T | p.Gly398Cys | missense_variant | 18/38 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL1A1 | ENST00000225964.10 | c.2110G>T | p.Gly704Cys | missense_variant | 31/51 | 1 | NM_000088.4 | P1 | |
COL1A1 | ENST00000476387.1 | n.459G>T | non_coding_transcript_exon_variant | 7/9 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1438718Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 713518
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Osteogenesis imperfecta type III Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 1989 | - - |
Osteogenesis imperfecta with normal sclerae, dominant form Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Department of Medical Sciences, Uppsala University | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at