chr20-419671-C-CGACGAGG
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The ENST00000356286.10(RBCK1):c.697_703dup(p.Glu235GlyfsTer67) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000759 in 1,581,270 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. P232P) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
ENST00000356286.10 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RBCK1 | NM_031229.4 | c.697_703dup | p.Glu235GlyfsTer67 | frameshift_variant | 6/12 | ENST00000356286.10 | NP_112506.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RBCK1 | ENST00000356286.10 | c.697_703dup | p.Glu235GlyfsTer67 | frameshift_variant | 6/12 | 1 | NM_031229.4 | ENSP00000348632 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152222Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000208 AC: 4AN: 192174Hom.: 0 AF XY: 0.0000383 AC XY: 4AN XY: 104500
GnomAD4 exome AF: 0.00000770 AC: 11AN: 1429048Hom.: 0 Cov.: 32 AF XY: 0.00000847 AC XY: 6AN XY: 708612
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74374
ClinVar
Submissions by phenotype
Polyglucosan body myopathy type 1 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 20, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 140630). This variant is also known as p.E190fs. This premature translational stop signal has been observed in individual(s) with progressive muscular weakness and cardiomyopathy (PMID: 23889995). This variant is present in population databases (rs730880330, gnomAD 0.03%). This sequence change creates a premature translational stop signal (p.Glu235Glyfs*67) in the RBCK1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RBCK1 are known to be pathogenic (PMID: 2379848, 23104095, 23889995). - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Apr 30, 2022 | - - |
Polyglucosan body myopathy 1 without immunodeficiency Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at