rs1553940073
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_000232.5(SGCB):c.707G>A(p.Gly236Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G236G) has been classified as Likely benign.
Frequency
Consequence
NM_000232.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SGCB | NM_000232.5 | c.707G>A | p.Gly236Asp | missense_variant | 5/6 | ENST00000381431.10 | |
SGCB | XM_047416074.1 | c.497G>A | p.Gly166Asp | missense_variant | 4/5 | ||
SGCB | XM_047416075.1 | c.410G>A | p.Gly137Asp | missense_variant | 4/5 | ||
SGCB | XM_047416076.1 | c.410G>A | p.Gly137Asp | missense_variant | 4/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SGCB | ENST00000381431.10 | c.707G>A | p.Gly236Asp | missense_variant | 5/6 | 1 | NM_000232.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461294Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 726990
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2E Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 13, 2018 | This sequence change replaces glycine with aspartic acid at codon 236 of the SGCB protein (p.Gly236Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a SGCB-related disease. In summary, this variant is a novel missense change with uncertain impact on protein function. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at