4-52028063-CTT-C
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Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_000232.5(SGCB):βc.656_657delβ(p.Lys219SerfsTer2) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000062 in 1,613,288 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (β β ).
Frequency
Genomes: π 0.000039 ( 0 hom., cov: 33)
Exomes π: 0.0000027 ( 0 hom. )
Consequence
SGCB
NM_000232.5 frameshift
NM_000232.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.02
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 14 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 7 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 4-52028063-CTT-C is Pathogenic according to our data. Variant chr4-52028063-CTT-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 466603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SGCB | NM_000232.5 | c.656_657del | p.Lys219SerfsTer2 | frameshift_variant | 5/6 | ENST00000381431.10 | |
SGCB | XM_047416074.1 | c.446_447del | p.Lys149SerfsTer2 | frameshift_variant | 4/5 | ||
SGCB | XM_047416075.1 | c.359_360del | p.Lys120SerfsTer2 | frameshift_variant | 4/5 | ||
SGCB | XM_047416076.1 | c.359_360del | p.Lys120SerfsTer2 | frameshift_variant | 4/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SGCB | ENST00000381431.10 | c.656_657del | p.Lys219SerfsTer2 | frameshift_variant | 5/6 | 1 | NM_000232.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152156Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461132Hom.: 0 AF XY: 0.00000413 AC XY: 3AN XY: 726946
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152156Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74352
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ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2E Pathogenic:5
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 05, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | This sequence change creates a premature translational stop signal (p.Lys219Serfs*2) in the SGCB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SGCB are known to be pathogenic (PMID: 15938573, 18285821). This variant is present in population databases (no rsID available, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with SGCB-related conditions. ClinVar contains an entry for this variant (Variation ID: 466603). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jul 11, 2023 | - - |
Likely pathogenic, no assertion criteria provided | clinical testing | Counsyl | Apr 06, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 30, 2024 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at