rs779028054
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_004369.4(COL6A3):c.3598G>T(p.Val1200Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,614,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign 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. V1200V) has been classified as Likely benign.
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.3598G>T | p.Val1200Phe | missense_variant | 8/44 | ENST00000295550.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A3 | ENST00000295550.9 | c.3598G>T | p.Val1200Phe | missense_variant | 8/44 | 1 | NM_004369.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251274Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135888
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461832Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727230
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74344
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Sep 30, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 17, 2017 | The V1200F variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The V1200F variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. - |
Bethlem myopathy 1A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 02, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at