rs17314986

Variant names:

• chr13-23250679-G-A
• rs17314986
• NM_000231.3:c.347G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

This summary comes from the ClinGen Evidence Repository: The NM_000231.3: c.347G>A variant in SGCG is a missense variant predicted to cause substitution of arginine by histidine at amino acid 116, p.(Arg116His). The filtering allele frequency for this variant is 0.1550 in gnomAD v4.1.0 exomes (the lower threshold of the 95% confidence interval of 944/5768 Middle Eastern chromosomes), which is greater than the LGMD VCEP threshold for BA1, meeting this criterion (BA1). This variant was reported in a single heterozygous state in a patient with sarcoglycanopathy who also had a compound heterozygous pair of variants in SGCA that were considered diagnostic (PMID:18421900). The REVEL score for this variant is 0.375 and the SpliceAI score is 0.01 (BP4, PP3 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; 06/25/2025): BA1. LINK:https://erepo.genome.network/evrepo/ui/classification/CA145903/MONDO:0015152/185

• Frequency:
  • Genomes: 𝑓 0.10 (973 hom., cov: 33)
  • Exomes 𝑓: 0.13 (12307 hom.)
• Consequence: SGCG NM_001378244.1 missense
• Clinical Significance: Benign reviewed by expert panel B:16
• Conservation: PhyloP100: 3.16
• Publications: 28 publications found

Genes affected

SGCG (HGNC:10809): (sarcoglycan gamma) This gene encodes gamma-sarcoglycan, one of several sarcolemmal transmembrane glycoproteins that interact with dystrophin. The dystrophin-glycoprotein complex (DGC) spans the sarcolemma and is comprised of dystrophin, syntrophin, alpha- and beta-dystroglycans and sarcoglycans. The DGC provides a structural link between the subsarcolemmal cytoskeleton and the extracellular matrix of muscle cells. Defects in the encoded protein can lead to early onset autosomal recessive muscular dystrophy, in particular limb-girdle muscular dystrophy, type 2C (LGMD2C). [provided by RefSeq, Oct 2008]

SGCG Gene-Disease associations (from GenCC):

• autosomal recessive limb-girdle muscular dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive limb-girdle muscular dystrophy type 2C

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378244.1. 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
	SGCG	NM_000231.3	MANE Select	c.347G>A	p.Arg116His	missense	Exon 4 of 8	NP_000222.2
	SGCG	NM_001378244.1		c.401G>A	p.Arg134His	missense	Exon 4 of 8	NP_001365173.1
	SGCG	NM_001378245.1		c.347G>A	p.Arg116His	missense	Exon 5 of 9	NP_001365174.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCG	ENST00000218867.4	TSL:1 MANE Select	c.347G>A	p.Arg116His	missense	Exon 4 of 8	ENSP00000218867.3
	SGCG	ENST00000942469.1		c.347G>A	p.Arg116His	missense	Exon 4 of 9	ENSP00000612528.1
	SGCG	ENST00000876364.1		c.347G>A	p.Arg116His	missense	Exon 5 of 9	ENSP00000546423.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15327 AN: 152054 Hom.: 973 Cov.: 33

Gnomad AFR AF: 0.0304

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.0123

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.123

GnomAD2 exomes AF: 0.112 AC: 28207 AN: 251024 AF XY: 0.117

Gnomad AFR exome AF: 0.0273

Gnomad AMR exome AF: 0.0875

Gnomad ASJ exome AF: 0.165

Gnomad EAS exome AF: 0.0129

Gnomad FIN exome AF: 0.154

Gnomad NFE exome AF: 0.130

Gnomad OTH exome AF: 0.127

GnomAD4 exome AF: 0.126 AC: 183159 AN: 1458844 Hom.: 12307 Cov.: 31 AF XY: 0.126 AC XY: 91775 AN XY: 725820

African (AFR) AF: 0.0281 AC: 939 AN: 33442

American (AMR) AF: 0.0893 AC: 3993 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 4291 AN: 26112

East Asian (EAS) AF: 0.0136 AC: 539 AN: 39686

South Asian (SAS) AF: 0.129 AC: 11115 AN: 86114

European-Finnish (FIN) AF: 0.146 AC: 7770 AN: 53380

Middle Eastern (MID) AF: 0.164 AC: 944 AN: 5768

European-Non Finnish (NFE) AF: 0.132 AC: 146134 AN: 1109348

Other (OTH) AF: 0.123 AC: 7434 AN: 60292

GnomAD4 genome AF: 0.101 AC: 15322 AN: 152172 Hom.: 973 Cov.: 33 AF XY: 0.103 AC XY: 7666 AN XY: 74380

African (AFR) AF: 0.0303 AC: 1259 AN: 41518

American (AMR) AF: 0.103 AC: 1568 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 551 AN: 3470

East Asian (EAS) AF: 0.0123 AC: 64 AN: 5190

South Asian (SAS) AF: 0.130 AC: 627 AN: 4818

European-Finnish (FIN) AF: 0.155 AC: 1638 AN: 10554

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9127 AN: 68010

Other (OTH) AF: 0.122 AC: 257 AN: 2110

Alfa AF: 0.120 Hom.: 4273

Bravo AF: 0.0931

TwinsUK AF: 0.126 AC: 467

ALSPAC AF: 0.135 AC: 521

ESP6500AA AF: 0.0304 AC: 134

ESP6500EA AF: 0.139 AC: 1198

ExAC AF: 0.110 AC: 13312

Asia WGS AF: 0.0690 AC: 240 AN: 3478

EpiCase AF: 0.134

EpiControl AF: 0.136

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	-	7	not specified (7)
-	-	5	Autosomal recessive limb-girdle muscular dystrophy type 2C (5)
-	-	1	Autosomal recessive limb-girdle muscular dystrophy (1)
-	-	1	Limb-girdle muscular dystrophy, recessive (1)
-	-	1	not provided (1)
-	-	1	Sarcoglycanopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.10
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.93	D
Eigen	Benign	0.034
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.79	T
MetaRNN	Benign	0.0037	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		3.2
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.99	D
Vest4		0.23
MPC		0.42
ClinPred		0.035	T
GERP RS		3.5
Varity_R		0.38
gMVP		0.69
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17314986; hg19: chr13-23824818; COSMIC: COSV107263536; COSMIC: COSV107263536;