rs755342579
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM1PP2
The NM_004370.6(COL12A1):c.8369C>T(p.Pro2790Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000007 in 1,572,280 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P2790S) has been classified as Uncertain significance.
Frequency
Consequence
NM_004370.6 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL12A1 | NM_004370.6 | c.8369C>T | p.Pro2790Leu | missense_variant | 56/66 | ENST00000322507.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL12A1 | ENST00000322507.13 | c.8369C>T | p.Pro2790Leu | missense_variant | 56/66 | 1 | NM_004370.6 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152130Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000183 AC: 4AN: 218954Hom.: 0 AF XY: 0.0000167 AC XY: 2AN XY: 119978
GnomAD4 exome AF: 0.00000634 AC: 9AN: 1420150Hom.: 0 Cov.: 30 AF XY: 0.00000283 AC XY: 2AN XY: 706340
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74310
ClinVar
Submissions by phenotype
Bethlem myopathy 2;C4225314:Ullrich congenital muscular dystrophy 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 27, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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) performed at Invitae indicates that this missense variant is not expected to disrupt COL12A1 protein function. ClinVar contains an entry for this variant (Variation ID: 475899). This variant has not been reported in the literature in individuals affected with COL12A1-related conditions. This variant is present in population databases (rs755342579, gnomAD 0.009%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 2790 of the COL12A1 protein (p.Pro2790Leu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at