rs150694150
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_004369.4(COL6A3):c.5825C>T(p.Pro1942Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000057 in 1,614,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. P1942A) has been classified as Uncertain significance.
Frequency
Consequence
NM_004369.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A3 | NM_004369.4 | c.5825C>T | p.Pro1942Leu | missense_variant | 12/44 | ENST00000295550.9 | |
COL6A3 | NM_057167.4 | c.5207C>T | p.Pro1736Leu | missense_variant | 11/43 | ||
COL6A3 | NM_057166.5 | c.4004C>T | p.Pro1335Leu | missense_variant | 9/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A3 | ENST00000295550.9 | c.5825C>T | p.Pro1942Leu | missense_variant | 12/44 | 1 | NM_004369.4 | P1 | |
COL6A3 | ENST00000472056.5 | c.4004C>T | p.Pro1335Leu | missense_variant | 9/41 | 1 | |||
COL6A3 | ENST00000353578.9 | c.5207C>T | p.Pro1736Leu | missense_variant | 11/43 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000986 AC: 15AN: 152194Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000120 AC: 30AN: 250324Hom.: 0 AF XY: 0.0000665 AC XY: 9AN XY: 135404
GnomAD4 exome AF: 0.0000527 AC: 77AN: 1461826Hom.: 0 Cov.: 32 AF XY: 0.0000413 AC XY: 30AN XY: 727208
GnomAD4 genome ? AF: 0.0000986 AC: 15AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74354
ClinVar
Submissions by phenotype
not provided Uncertain:4
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 30, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 17, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 25, 2023 | Identified in the heterozygous state in a patient with limb-girdle muscular dystrophy in published literature and reported as a variant of uncertain significance (Nallamilli et al., 2018); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30564623) - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2021 | - - |
Ullrich congenital muscular dystrophy 1A;C4225336:Dystonia 27;CN029274:Bethlem myopathy 1A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Bethlem myopathy 1A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at