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

Genomes: 𝑓 0.0024 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

SGCB
NM_000232.5 missense

Scores

1
18

Clinical Significance

Benign reviewed by expert panel U:1B:6

Conservation

PhyloP100: 0.805
Variant links:
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 Benign. Variant got -8 ACMG points.

BA1
For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SGCBNM_000232.5 linkc.92G>T p.Ser31Ile missense_variant 2/6 ENST00000381431.10 NP_000223.1 Q16585-1Q5U0N0
SGCBXM_047416074.1 linkc.34-3719G>T intron_variant XP_047272030.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SGCBENST00000381431.10 linkc.92G>T p.Ser31Ile missense_variant 2/61 NM_000232.5 ENSP00000370839.6 Q16585-1
SGCBENST00000506357.5 linkn.77G>T non_coding_transcript_exon_variant 2/55 ENSP00000421235.1 H0Y8J3
SGCBENST00000514133.1 linkn.59G>T non_coding_transcript_exon_variant 1/45 ENSP00000425818.1 H0YA15

Frequencies

GnomAD3 genomes
AF:
0.00242
AC:
368
AN:
152170
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00838
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00118
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000497
AC:
125
AN:
251468
Hom.:
0
AF XY:
0.000383
AC XY:
52
AN XY:
135910
show subpopulations
Gnomad AFR exome
AF:
0.00701
Gnomad AMR exome
AF:
0.000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000223
AC:
326
AN:
1461660
Hom.:
0
Cov.:
31
AF XY:
0.000165
AC XY:
120
AN XY:
727140
show subpopulations
Gnomad4 AFR exome
AF:
0.00806
Gnomad4 AMR exome
AF:
0.000470
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.000381
GnomAD4 genome
AF:
0.00242
AC:
369
AN:
152288
Hom.:
2
Cov.:
32
AF XY:
0.00234
AC XY:
174
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.00840
Gnomad4 AMR
AF:
0.00111
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.000396
Hom.:
0
Bravo
AF:
0.00249
ESP6500AA
AF:
0.00590
AC:
26
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000626
AC:
76
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Uncertain:1Benign:6
Revision: reviewed by expert panel
LINK: link

Submissions by phenotype

not specified Benign:2
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)May 29, 2013- -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
not provided Benign:2
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Likely benign, criteria provided, single submitterclinical testingAthena DiagnosticsMar 12, 2020- -
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 07, 2021The 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 panelcurationClinGen Limb Girdle Muscular Dystrophy Variant Curation Expert Panel, ClinGenJan 09, 2025The 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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
18
DANN
Benign
0.97
DEOGEN2
Benign
0.38
T
Eigen
Benign
-0.86
Eigen_PC
Benign
-0.77
FATHMM_MKL
Benign
0.39
N
LIST_S2
Benign
0.77
T
M_CAP
Benign
0.060
D
MetaRNN
Benign
0.0080
T
MetaSVM
Benign
-0.59
T
MutationAssessor
Benign
0.55
N
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.18
Sift
Benign
0.11
T
Sift4G
Benign
0.13
T
Polyphen
0.0060
B
Vest4
0.22
MVP
0.68
MPC
0.089
ClinPred
0.0079
T
GERP RS
4.1
Varity_R
0.058
gMVP
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs115928999; hg19: chr4-52899748; API