rs1188543260
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP2PP3
The NM_004370.6(COL12A1):āc.3034A>Gā(p.Met1012Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,461,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M1012T) has been classified as Uncertain significance.
Frequency
Consequence
NM_004370.6 missense
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 | UniProt |
---|---|---|---|---|---|---|---|
COL12A1 | NM_004370.6 | c.3034A>G | p.Met1012Val | missense_variant | 15/66 | ENST00000322507.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL12A1 | ENST00000322507.13 | c.3034A>G | p.Met1012Val | missense_variant | 15/66 | 1 | NM_004370.6 | P4 | |
COL12A1 | ENST00000345356.10 | c.74-3991A>G | intron_variant | 1 | |||||
COL12A1 | ENST00000483888.6 | c.3034A>G | p.Met1012Val | missense_variant | 15/65 | 5 | A1 | ||
COL12A1 | ENST00000416123.6 | c.3034A>G | p.Met1012Val | missense_variant | 14/63 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461536Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 727070
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 | Feb 12, 2018 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with COL12A1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with valine at codon 1012 of the COL12A1 protein (p.Met1012Val). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and valine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at