rs17314986

Variant names:

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_000231.3 missense

Scores

Clinical Significance

Benign reviewed by expert panel B:16

Conservation

PhyloP100: 3.16

Publications

28 publications found

Variant links:

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

SGCG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCG	NM_000231.3 link	c.347G>A	p.Arg116His	missense_variant	Exon 4 of 8	ENST00000218867.4	NP_000222.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCG	ENST00000218867.4 link	c.347G>A	p.Arg116His	missense_variant	Exon 4 of 8	1	NM_000231.3	ENSP00000218867.3

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15327

AN:

152054

Hom.:

973

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.126

AC XY:

91775

AN XY:

725820

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

7609

15217

22826

30434

38043

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5228

10456

15684

20912

26140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.101

AC:

15322

AN:

152172

Hom.:

973

Cov.:

AF XY:

0.103

AC XY:

7666

AN XY:

74380

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.134

AC:

9127

AN:

68010

Other (OTH)

AF:

0.122

AC:

257

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

709

1418

2126

2835

3544

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

182

364

546

728

910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Significance: Benign

Submissions summary: Benign:16

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not specified

Benign:7

Apr 23, 2021

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 07, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Dec 03, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 26, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Nov 26, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Arg116His in exon 4 of SGCG: This variant is not expected to have clinical sig nificance because it has been identified in 14% (1198/8600) of European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu /EVS/; dbSNP rs17314986). -

Autosomal recessive limb-girdle muscular dystrophy type 2C

Benign:5

Jul 01, 2021

Pars Genome Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 31, 2018

SIB Swiss Institute of Bioinformatics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

This variant is interpreted as a Benign - Stand Alone, for Muscular dystrophy, limb-girdle, type 2C, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BA1 => Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. -

Autosomal recessive limb-girdle muscular dystrophy

Benign:1

Jun 25, 2025

ClinGen Limb Girdle Muscular Dystrophy Variant Curation Expert Panel, ClinGen

Significance:Benign

Review Status:reviewed by expert panel

Collection Method:curation

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. -

Limb-girdle muscular dystrophy, recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sarcoglycanopathy

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.10

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.93

Eigen

Benign

0.034

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.79

MetaRNN

Benign

0.0037

MetaSVM

Benign

-0.74

MutationAssessor

Pathogenic

3.1

PhyloP100

3.2

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-4.3

REVEL

Uncertain

0.38

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0020

Polyphen

0.99

Vest4

0.23

MPC

0.42

ClinPred

0.035

GERP RS

3.5

Varity_R

0.38

gMVP

0.69

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over