chr6-75087675-C-T
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP2BP4_StrongBP6BS1BS2
The NM_004370.6(COL12A1):c.9083G>A(p.Arg3028His) variant causes a missense change. The variant allele was found at a frequency of 0.00566 in 1,610,232 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R3028C) has been classified as Uncertain significance.
Frequency
Consequence
NM_004370.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL12A1 | NM_004370.6 | c.9083G>A | p.Arg3028His | missense_variant | 65/66 | ENST00000322507.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL12A1 | ENST00000322507.13 | c.9083G>A | p.Arg3028His | missense_variant | 65/66 | 1 | NM_004370.6 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00462 AC: 703AN: 152130Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.00407 AC: 996AN: 244726Hom.: 9 AF XY: 0.00413 AC XY: 549AN XY: 132950
GnomAD4 exome AF: 0.00577 AC: 8412AN: 1457984Hom.: 41 Cov.: 34 AF XY: 0.00564 AC XY: 4088AN XY: 725302
GnomAD4 genome AF: 0.00461 AC: 702AN: 152248Hom.: 2 Cov.: 32 AF XY: 0.00443 AC XY: 330AN XY: 74440
ClinVar
Submissions by phenotype
not provided Benign:5
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 14, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | COL12A1: BS2 - |
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 29, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 14, 2021 | The c.9083G>A (p.R3028H) alteration is located in exon 65 (coding exon 64) of the COL12A1 gene. This alteration results from a G to A substitution at nucleotide position 9083, causing the arginine (R) at amino acid position 3028 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Bethlem myopathy 2;C4225314:Ullrich congenital muscular dystrophy 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Ullrich congenital muscular dystrophy 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at