rs66527965
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM2PM5PP2PP3_StrongPP5_Moderate
The NM_000088.4(COL1A1):c.1777G>T(p.Gly593Cys) 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. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G593D) has been classified as Pathogenic.
Frequency
Consequence
NM_000088.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL1A1 | NM_000088.4 | c.1777G>T | p.Gly593Cys | missense_variant | 26/51 | ENST00000225964.10 | NP_000079.2 | |
COL1A1 | XM_011524341.2 | c.1579G>T | p.Gly527Cys | missense_variant | 23/48 | XP_011522643.1 | ||
COL1A1 | XM_005257058.5 | c.1777G>T | p.Gly593Cys | missense_variant | 26/49 | XP_005257115.2 | ||
COL1A1 | XM_005257059.5 | c.958-345G>T | intron_variant | XP_005257116.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL1A1 | ENST00000225964.10 | c.1777G>T | p.Gly593Cys | missense_variant | 26/51 | 1 | NM_000088.4 | ENSP00000225964.6 | ||
COL1A1 | ENST00000476387.1 | n.126G>T | non_coding_transcript_exon_variant | 2/9 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 34
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Infantile cortical hyperostosis;C0023931:Osteogenesis imperfecta type I;C0029456:Osteoporosis;C0268358:Osteogenesis imperfecta, perinatal lethal;C0268362:Osteogenesis imperfecta type III;C0268363:Osteogenesis imperfecta with normal sclerae, dominant form;C4551623:Ehlers-Danlos syndrome, arthrochalasia type;C5436842:Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Juno Genomics, Hangzhou Juno Genomics, Inc | - | PM2_Supporting+PP3+PS4_Supporting+PS2_Supporting+PP2+PP4 - |
Osteogenesis imperfecta, type III/IV Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 1991 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at