rs778403814
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_004369.4(COL6A3):c.3220G>A(p.Asp1074Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004369.4 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 |
---|---|---|---|---|---|---|---|
COL6A3 | NM_004369.4 | c.3220G>A | p.Asp1074Asn | missense_variant | 8/44 | ENST00000295550.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A3 | ENST00000295550.9 | c.3220G>A | p.Asp1074Asn | missense_variant | 8/44 | 1 | NM_004369.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152024Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250242Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135352
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461846Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727230
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152024Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74228
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 03, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2022 | COL6A3: BP4 - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 04, 2020 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 30564623) - |
Bethlem myopathy 1A Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Mar 05, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 29, 2023 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 23, 2023 | The c.3220G>A (p.D1074N) alteration is located in exon 8 (coding exon 7) of the COL6A3 gene. This alteration results from a G to A substitution at nucleotide position 3220, causing the aspartic acid (D) at amino acid position 1074 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Dystonia 27 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 1A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Mar 05, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at