rs1554171436
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_004370.6(COL12A1):c.6916C>T(p.Pro2306Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,455,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. P2306L) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL12A1 | NM_004370.6 | c.6916C>T | p.Pro2306Ser | missense_variant | 43/66 | ENST00000322507.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL12A1 | ENST00000322507.13 | c.6916C>T | p.Pro2306Ser | missense_variant | 43/66 | 1 | NM_004370.6 | P4 | |
COL12A1 | ENST00000345356.10 | c.3424C>T | p.Pro1142Ser | missense_variant | 28/51 | 1 | |||
COL12A1 | ENST00000483888.6 | c.6916C>T | p.Pro2306Ser | missense_variant | 43/65 | 5 | A1 | ||
COL12A1 | ENST00000416123.6 | c.6916C>T | p.Pro2306Ser | missense_variant | 42/63 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1455106Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 723082
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Bethlem myopathy 2;C4225314:Ullrich congenital muscular dystrophy 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 22, 2023 | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 2306 of the COL12A1 protein (p.Pro2306Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with COL12A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 475892). 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 COL12A1 protein function. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at