chr21-46003438-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP6
The NM_001848.3(COL6A1):c.2512G>A(p.Ala838Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000033 in 1,603,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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_001848.3 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL6A1 | NM_001848.3 | c.2512G>A | p.Ala838Thr | missense_variant | Exon 35 of 35 | ENST00000361866.8 | NP_001839.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152224Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000510 AC: 12AN: 235344Hom.: 0 AF XY: 0.0000616 AC XY: 8AN XY: 129918
GnomAD4 exome AF: 0.0000331 AC: 48AN: 1451400Hom.: 0 Cov.: 37 AF XY: 0.0000374 AC XY: 27AN XY: 722584
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152342Hom.: 0 Cov.: 34 AF XY: 0.0000268 AC XY: 2AN XY: 74500
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.2512G>A (p.A838T) alteration is located in exon 35 (coding exon 35) of the COL6A1 gene. This alteration results from a G to A substitution at nucleotide position 2512, causing the alanine (A) at amino acid position 838 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
The A838T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The A838T 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 non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals; however, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with COL6A1-related disorders (Stenson et al., 2014). In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. -
not specified Benign:1
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Bethlem myopathy 1A Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at