rs72656353
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP2PP3_ModeratePP5_Moderate
The NM_000088.4(COL1A1):c.4391T>C(p.Leu1464Pro) variant causes a missense change involving the alteration of a non-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 Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. L1464L) has been classified as Likely benign.
Frequency
Consequence
NM_000088.4 missense
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL1A1 | NM_000088.4 | c.4391T>C | p.Leu1464Pro | missense_variant | 51/51 | ENST00000225964.10 | |
COL1A1 | XM_011524341.2 | c.4193T>C | p.Leu1398Pro | missense_variant | 48/48 | ||
COL1A1 | XM_005257058.5 | c.4121T>C | p.Leu1374Pro | missense_variant | 49/49 | ||
COL1A1 | XM_005257059.5 | c.3473T>C | p.Leu1158Pro | missense_variant | 38/38 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL1A1 | ENST00000225964.10 | c.4391T>C | p.Leu1464Pro | missense_variant | 51/51 | 1 | NM_000088.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 29
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 29
ClinVar
Submissions by phenotype
Osteogenesis imperfecta type III Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 1996 | - - |
Osteogenesis imperfecta type I Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 11, 2023 | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1464 of the COL1A1 protein (p.Leu1464Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with osteogenesis imperfecta (PMID: 8723681, 27509835, 27519266). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 17332). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on COL1A1 protein function. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at