rs114248590
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_004369.4(COL6A3):c.7173C>T(p.Tyr2391=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000948 in 1,614,072 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004369.4 splice_region, synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A3 | NM_004369.4 | c.7173C>T | p.Tyr2391= | splice_region_variant, synonymous_variant | 35/44 | ENST00000295550.9 | |
COL6A3 | NM_057167.4 | c.6555C>T | p.Tyr2185= | splice_region_variant, synonymous_variant | 34/43 | ||
COL6A3 | NM_057166.5 | c.5352C>T | p.Tyr1784= | splice_region_variant, synonymous_variant | 32/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A3 | ENST00000295550.9 | c.7173C>T | p.Tyr2391= | splice_region_variant, synonymous_variant | 35/44 | 1 | NM_004369.4 | P1 | |
COL6A3 | ENST00000472056.5 | c.5352C>T | p.Tyr1784= | splice_region_variant, synonymous_variant | 32/41 | 1 | |||
COL6A3 | ENST00000353578.9 | c.6555C>T | p.Tyr2185= | splice_region_variant, synonymous_variant | 34/43 | 5 | |||
COL6A3 | ENST00000491769.1 | n.1427C>T | splice_region_variant, non_coding_transcript_exon_variant | 12/20 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 20AN: 152132Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000152 AC: 38AN: 250678Hom.: 0 AF XY: 0.000184 AC XY: 25AN XY: 135564
GnomAD4 exome AF: 0.0000903 AC: 132AN: 1461822Hom.: 1 Cov.: 34 AF XY: 0.000110 AC XY: 80AN XY: 727216
GnomAD4 genome AF: 0.000138 AC: 21AN: 152250Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74436
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 06, 2018 | - - |
Bethlem myopathy 1A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
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