NM_000232.5:c.799C>T

Variant names:

• chr4-52024115-G-A
• rs200761715
• NM_000232.5:c.799C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3 BA1

This summary comes from the ClinGen Evidence Repository: The NM_000232.5: c.799C>T variant in SGCB is a missense variant predicted to cause substitution of arginine by cysteine at amino acid 267 (p.Arg267Cys). The filtering allele frequency of this variant is 0.01396 in the South Asian population in gnomAD v2.1.1 (the lower threshold of the 95% CI of 462/30614 exome 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 0.75, which exceeds the threshold of ≥0.70, evidence that correlates with impact to DYSF function (PP3). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive limb girdle muscular dystrophy. Although there are both pathogenic and benign types of evidence for this variant, the predictive pathogenic evidence is not considered inconsistent with the final classification. ACMG/AMP criteria applied, as specified by the ClinGen LGMD VCEP (LGMD VCEP specifications version 1.0.0; 01/09/2025): BA1, PP3. LINK:https://erepo.genome.network/evrepo/ui/classification/CA2918272/MONDO:0015152/184

• Frequency:
  • Genomes: 𝑓 0.00055 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (28 hom.)
• Consequence: SGCB NM_000232.5 missense
• Clinical Significance: Benign reviewed by expert panel U:1 B:10
• Conservation: PhyloP100: 7.90
• Publications: 4 publications found

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]

SGCB Gene-Disease associations (from GenCC):

• autosomal recessive limb-girdle muscular dystrophy

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, PanelApp Australia
• autosomal recessive limb-girdle muscular dystrophy type 2E

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Myriad Women’s Health, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• PP3: For more information check the summary or visit ClinGen Evidence Repository.
• BA1: For more information check the summary or visit ClinGen Evidence Repository.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000232.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCB	NM_000232.5	MANE Select	c.799C>T	p.Arg267Cys	missense	Exon 6 of 6	NP_000223.1	Q5U0N0
	SGCB	NM_001440519.1		c.589C>T	p.Arg197Cys	missense	Exon 5 of 5	NP_001427448.1
	SGCB	NM_001440520.1		c.502C>T	p.Arg168Cys	missense	Exon 7 of 7	NP_001427449.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCB	ENST00000381431.10	TSL:1 MANE Select	c.799C>T	p.Arg267Cys	missense	Exon 6 of 6	ENSP00000370839.6	Q16585-1
	SGCB	ENST00000899666.1		c.787C>T	p.Arg263Cys	missense	Exon 6 of 6	ENSP00000569725.1
	SGCB	ENST00000912466.1		c.667C>T	p.Arg223Cys	missense	Exon 5 of 5	ENSP00000582525.1

Frequencies

GnomAD3 genomes AF: 0.000565 AC: 86 AN: 152158 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0141

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00203 AC: 511 AN: 251442 AF XY: 0.00269

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000237

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00107 AC: 1564 AN: 1461808 Hom.: 28 Cov.: 31 AF XY: 0.00150 AC XY: 1092 AN XY: 727210

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.000268 AC: 12 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39696

South Asian (SAS) AF: 0.0150 AC: 1298 AN: 86252

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53412

Middle Eastern (MID) AF: 0.00470 AC: 27 AN: 5742

European-Non Finnish (NFE) AF: 0.000131 AC: 146 AN: 1111976

Other (OTH) AF: 0.00118 AC: 71 AN: 60392

GnomAD4 genome AF: 0.000552 AC: 84 AN: 152276 Hom.: 0 Cov.: 32 AF XY: 0.000779 AC XY: 58 AN XY: 74458

African (AFR) AF: 0.0000241 AC: 1 AN: 41558

American (AMR) AF: 0.000392 AC: 6 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.0137 AC: 66 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000242 Hom.: 0

Bravo AF: 0.000223

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00222 AC: 269

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Benign

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	-	3	Autosomal recessive limb-girdle muscular dystrophy type 2E (3)
-	-	3	not specified (3)
-	-	1	Autosomal recessive limb-girdle muscular dystrophy (1)
-	-	1	Hypertrophic cardiomyopathy (1)
-	1	-	Limb-girdle muscular dystrophy, recessive (1)
-	-	1	not provided (1)
-	-	1	Qualitative or quantitative defects of beta-sarcoglycan (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.92	D
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
MetaRNN	Benign	0.013	T
MetaSVM	Pathogenic	0.93	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.9
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.9	D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.71
MVP		0.95
MPC		0.42
ClinPred		0.10	T
GERP RS		5.4
Varity_R		0.37
gMVP		0.68
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs200761715; hg19: chr4-52890281;