rs747200439
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004369.4(COL6A3):c.5534G>T(p.Gly1845Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,613,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1845A) has been classified as Uncertain significance.
Frequency
Consequence
NM_004369.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A3 | NM_004369.4 | c.5534G>T | p.Gly1845Val | missense_variant | 12/44 | ENST00000295550.9 | |
COL6A3 | NM_057167.4 | c.4916G>T | p.Gly1639Val | missense_variant | 11/43 | ||
COL6A3 | NM_057166.5 | c.3713G>T | p.Gly1238Val | missense_variant | 9/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A3 | ENST00000295550.9 | c.5534G>T | p.Gly1845Val | missense_variant | 12/44 | 1 | NM_004369.4 | P1 | |
COL6A3 | ENST00000472056.5 | c.3713G>T | p.Gly1238Val | missense_variant | 9/41 | 1 | |||
COL6A3 | ENST00000353578.9 | c.4916G>T | p.Gly1639Val | missense_variant | 11/43 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152158Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 247902Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134700
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461512Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727062
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74324
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 29, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 27, 2016 | - - |
Bethlem myopathy 1A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 28, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COL6A3 protein function. ClinVar contains an entry for this variant (Variation ID: 497149). This variant has not been reported in the literature in individuals affected with COL6A3-related conditions. This variant is present in population databases (rs747200439, gnomAD 0.0009%). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1845 of the COL6A3 protein (p.Gly1845Val). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at