chr4-52033582-C-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1
This summary comes from the ClinGen Evidence Repository: The NM_000232.5: c.92G>T variant in SGCB is a missense variant predicted to cause substitution of serine by isoleucine at amino acid 31 (p.Ser31Ile). The filtering allele frequency of this variant is 0.007653 in the African/African American population in gnomAD v3.1.2 (the lower threshold of the 95% CI of 347/41414 genome chromosomes), which is higher than the LGMD VCEP threshold (>0.002) for BA1 and therefore meets this criterion (BA1). The computational predictor REVEL gives a score of 0.18, which is above the LGMD VCEP threshold predicting a benign impact on sarcoglycan β function (<0.1; BP4 not met). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive limb girdle muscular dystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen LGMD VCEP (LGMD VCEP specifications version 1.0.0; 01/09/2025): BA1. LINK:https://erepo.genome.network/evrepo/ui/classification/CA145911/MONDO:0015152/184
Frequency
Consequence
NM_000232.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SGCB | ENST00000381431.10 | c.92G>T | p.Ser31Ile | missense_variant | 2/6 | 1 | NM_000232.5 | ENSP00000370839.6 | ||
SGCB | ENST00000506357.5 | n.77G>T | non_coding_transcript_exon_variant | 2/5 | 5 | ENSP00000421235.1 | ||||
SGCB | ENST00000514133.1 | n.59G>T | non_coding_transcript_exon_variant | 1/4 | 5 | ENSP00000425818.1 |
Frequencies
GnomAD3 genomes AF: 0.00242 AC: 368AN: 152170Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.000497 AC: 125AN: 251468Hom.: 0 AF XY: 0.000383 AC XY: 52AN XY: 135910
GnomAD4 exome AF: 0.000223 AC: 326AN: 1461660Hom.: 0 Cov.: 31 AF XY: 0.000165 AC XY: 120AN XY: 727140
GnomAD4 genome AF: 0.00242 AC: 369AN: 152288Hom.: 2 Cov.: 32 AF XY: 0.00234 AC XY: 174AN XY: 74476
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 29, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 12, 2020 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 07, 2021 | The c.92G>T (p.S31I) alteration is located in exon 2 (coding exon 2) of the SGCB gene. This alteration results from a G to T substitution at nucleotide position 92, causing the serine (S) at amino acid position 31 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Autosomal recessive limb-girdle muscular dystrophy Benign:1
Benign, reviewed by expert panel | curation | ClinGen Limb Girdle Muscular Dystrophy Variant Curation Expert Panel, ClinGen | Jan 09, 2025 | The NM_000232.5: c.92G>T variant in SGCB is a missense variant predicted to cause substitution of serine by isoleucine at amino acid 31 (p.Ser31Ile). The filtering allele frequency of this variant is 0.007653 in the African/African American population in gnomAD v3.1.2 (the lower threshold of the 95% CI of 347/41414 genome chromosomes), which is higher than the LGMD VCEP threshold (>0.002) for BA1 and therefore meets this criterion (BA1). The computational predictor REVEL gives a score of 0.18, which is above the LGMD VCEP threshold predicting a benign impact on sarcoglycan β function (<0.1; BP4 not met). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive limb girdle muscular dystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen LGMD VCEP (LGMD VCEP specifications version 1.0.0; 01/09/2025): BA1. - |
Autosomal recessive limb-girdle muscular dystrophy type 2E Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at