chr6-75156377-G-C
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_004370.6(COL12A1):āc.3130C>Gā(p.Pro1044Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,613,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign 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. P1044S) has been classified as Uncertain significance.
Frequency
Consequence
NM_004370.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL12A1 | NM_004370.6 | c.3130C>G | p.Pro1044Ala | missense_variant | 15/66 | ENST00000322507.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL12A1 | ENST00000322507.13 | c.3130C>G | p.Pro1044Ala | missense_variant | 15/66 | 1 | NM_004370.6 | P4 | |
COL12A1 | ENST00000345356.10 | c.74-3895C>G | intron_variant | 1 | |||||
COL12A1 | ENST00000483888.6 | c.3130C>G | p.Pro1044Ala | missense_variant | 15/65 | 5 | A1 | ||
COL12A1 | ENST00000416123.6 | c.3130C>G | p.Pro1044Ala | missense_variant | 14/63 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152126Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249348Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135266
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461690Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727144
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152244Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74446
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 07, 2019 | This sequence change replaces proline with alanine at codon 1044 of the COL12A1 protein (p.Pro1044Ala). The proline residue is moderately conserved and there is a small physicochemical difference between proline and alanine. This variant is present in population databases (rs200490883, ExAC 0.01%). This variant has not been reported in the literature in individuals with COL12A1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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