chr6-75180995-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP2PP3
The NM_004370.6(COL12A1):c.2108C>T(p.Ala703Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,613,834 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A703A) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL12A1 | NM_004370.6 | c.2108C>T | p.Ala703Val | missense_variant | 11/66 | ENST00000322507.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL12A1 | ENST00000322507.13 | c.2108C>T | p.Ala703Val | missense_variant | 11/66 | 1 | NM_004370.6 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151970Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249288Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135246
GnomAD4 exome AF: 0.0000192 AC: 28AN: 1461864Hom.: 0 Cov.: 32 AF XY: 0.0000206 AC XY: 15AN XY: 727232
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151970Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74222
ClinVar
Submissions by phenotype
Bethlem myopathy 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Mar 05, 2018 | - - |
Ullrich congenital muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Mar 05, 2018 | - - |
COL12A1-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 05, 2023 | The COL12A1 c.2108C>T variant is predicted to result in the amino acid substitution p.Ala703Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.011% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-75890711-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 30, 2019 | - - |
Bethlem myopathy 2;C4225314:Ullrich congenital muscular dystrophy 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 10, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at