rs116655315
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_004369.4(COL6A3):c.9116C>T(p.Thr3039Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000805 in 1,614,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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 -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL6A3 | NM_004369.4 | c.9116C>T | p.Thr3039Met | missense_variant | 41/44 | ENST00000295550.9 | NP_004360.2 | |
COL6A3 | NM_057167.4 | c.8498C>T | p.Thr2833Met | missense_variant | 40/43 | NP_476508.2 | ||
COL6A3 | NM_057166.5 | c.7295C>T | p.Thr2432Met | missense_variant | 38/41 | NP_476507.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL6A3 | ENST00000295550.9 | c.9116C>T | p.Thr3039Met | missense_variant | 41/44 | 1 | NM_004369.4 | ENSP00000295550.4 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152128Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000183 AC: 46AN: 251474Hom.: 0 AF XY: 0.000132 AC XY: 18AN XY: 135914
GnomAD4 exome AF: 0.0000821 AC: 120AN: 1461860Hom.: 0 Cov.: 60 AF XY: 0.0000729 AC XY: 53AN XY: 727222
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152248Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74446
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 24, 2024 | In silico analysis indicates that this missense 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) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 12, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 11, 2017 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 09, 2024 | The c.9116C>T (p.T3039M) alteration is located in exon 41 (coding exon 40) of the COL6A3 gene. This alteration results from a C to T substitution at nucleotide position 9116, causing the threonine (T) at amino acid position 3039 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Dystonia 27;C5935581:Bethlem myopathy 1C;C5935583:Ullrich congenital muscular dystrophy 1C Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 04, 2024 | - - |
Bethlem myopathy 1A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 22, 2023 | - - |
Collagen 6-related myopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at