rs200722892
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PM5BP6
The NM_004369.4(COL6A3):c.2302C>T(p.Arg768Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,614,234 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R768G) has been classified as Likely pathogenic.
Frequency
Consequence
NM_004369.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A3 | NM_004369.4 | c.2302C>T | p.Arg768Cys | missense_variant | 6/44 | ENST00000295550.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A3 | ENST00000295550.9 | c.2302C>T | p.Arg768Cys | missense_variant | 6/44 | 1 | NM_004369.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152232Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251356Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135880
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461884Hom.: 0 Cov.: 33 AF XY: 0.0000248 AC XY: 18AN XY: 727242
GnomAD4 genome ? AF: 0.0000656 AC: 10AN: 152350Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7AN XY: 74498
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 19, 2024 | The c.2302C>T (p.R768C) alteration is located in exon 6 (coding exon 5) of the COL6A3 gene. This alteration results from a C to T substitution at nucleotide position 2302, causing the arginine (R) at amino acid position 768 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Bethlem myopathy 1A Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jun 15, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at