rs536233725
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3
The NM_004370.6(COL12A1):c.5881G>A(p.Val1961Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,126 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 (★). Synonymous variant affecting the same amino acid position (i.e. V1961V) has been classified as Likely benign.
Frequency
Consequence
NM_004370.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL12A1 | NM_004370.6 | c.5881G>A | p.Val1961Met | missense_variant | 35/66 | ENST00000322507.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL12A1 | ENST00000322507.13 | c.5881G>A | p.Val1961Met | missense_variant | 35/66 | 1 | NM_004370.6 | P4 | |
COL12A1 | ENST00000345356.10 | c.2389G>A | p.Val797Met | missense_variant | 20/51 | 1 | |||
COL12A1 | ENST00000483888.6 | c.5881G>A | p.Val1961Met | missense_variant | 35/65 | 5 | A1 | ||
COL12A1 | ENST00000416123.6 | c.5881G>A | p.Val1961Met | missense_variant | 34/63 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249332Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135254
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461822Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1AN XY: 727206
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152304Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74476
ClinVar
Submissions by phenotype
Bethlem myopathy 2;C4225314:Ullrich congenital muscular dystrophy 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 05, 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 567669). This variant has not been reported in the literature in individuals affected with COL12A1-related conditions. This variant is present in population databases (rs536233725, gnomAD 0.003%). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1961 of the COL12A1 protein (p.Val1961Met). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at