6-75194833-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_004370.6(COL12A1):c.188C>G(p.Thr63Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_004370.6 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL12A1 | NM_004370.6 | c.188C>G | p.Thr63Arg | missense_variant, splice_region_variant | 3/66 | ENST00000322507.13 | NP_004361.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL12A1 | ENST00000322507.13 | c.188C>G | p.Thr63Arg | missense_variant, splice_region_variant | 3/66 | 1 | NM_004370.6 | ENSP00000325146.8 | ||
COL12A1 | ENST00000345356.10 | c.73+7887C>G | intron_variant | 1 | ENSP00000305147.9 | |||||
COL12A1 | ENST00000483888.6 | c.188C>G | p.Thr63Arg | missense_variant, splice_region_variant | 3/65 | 5 | ENSP00000421216.1 | |||
COL12A1 | ENST00000416123.6 | c.188C>G | p.Thr63Arg | missense_variant, splice_region_variant | 2/63 | 5 | ENSP00000412864.2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 28
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Bethlem myopathy 2;C4225314:Ullrich congenital muscular dystrophy 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 20, 2023 | This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 63 of the COL12A1 protein (p.Thr63Arg). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with COL12A1-related conditions. This variant is not present in population databases (gnomAD no frequency). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at