rs1553940687
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000232.5(SGCB):c.82_86del(p.Glu28LysfsTer5) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Genomes: not found (cov: 32)
Consequence
SGCB
NM_000232.5 frameshift
NM_000232.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.95
Genes affected
SGCB (HGNC:10806): (sarcoglycan beta) This gene encodes a member of the sarcoglycan family. Sarcoglycans are transmembrane components in the dystrophin-glycoprotein complex which help stabilize the muscle fiber membranes and link the muscle cytoskeleton to the extracellular matrix. Mutations in this gene have been associated with limb-girdle muscular dystrophy.[provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 103 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 4-52033587-TCTCTC-T is Pathogenic according to our data. Variant chr4-52033587-TCTCTC-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 466608.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-52033587-TCTCTC-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SGCB | NM_000232.5 | c.82_86del | p.Glu28LysfsTer5 | frameshift_variant | 2/6 | ENST00000381431.10 | |
SGCB | XM_047416074.1 | c.34-3729_34-3725del | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SGCB | ENST00000381431.10 | c.82_86del | p.Glu28LysfsTer5 | frameshift_variant | 2/6 | 1 | NM_000232.5 | P1 | |
SGCB | ENST00000506357.5 | c.68_72del | p.Glu24LysfsTer5 | frameshift_variant, NMD_transcript_variant | 2/5 | 5 | |||
SGCB | ENST00000514133.1 | c.49_53del | p.Glu17LysfsTer5 | frameshift_variant, NMD_transcript_variant | 1/4 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2E Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Feb 28, 2017 | For these reasons, this variant has been classified as Pathogenic. While this particular variant has not been reported in the literature, loss-of-function variants in SGCB are known to be pathogenic (PMID: 18285821). This sequence change deletes 5 nucleotides from exon 2 of the SGCB mRNA (c.82_86delGAGAG), causing a frameshift at codon 28. This creates a premature translational stop signal (p.Glu28Lysfs*5) and is expected to result in an absent or disrupted protein product. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Neuberg Centre For Genomic Medicine, NCGM | - | The frameshift variant c.82_86del (p.Glu28LysfsTer5) in SGCB gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Glu28LysfsTer5 variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant causes a frameshift starting with codon Glutamic Acid 28, changes this amino acid to Lysine residue, and creates a premature Stop codon at position 5 of the new reading frame, denoted p.Glu28LysfsTer5. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at