13-23185077-G-C

Variant names:

• chr13-23185077-G-C
• rs7322327
• NM_000231.3:c.-1+4002G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000231.3(SGCG):​c.-1+4002G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,048 control chromosomes in the GnomAD database, including 5,997 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (5997 hom., cov: 32)
• Consequence: SGCG NM_000231.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000231.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCG	NM_000231.3	MANE Select	c.-1+4002G>C		intron	N/A	NP_000222.2
	SGCG	NM_001378244.1		c.55-18618G>C		intron	N/A	NP_001365173.1
	SGCG	NM_001378245.1		c.-152+4094G>C		intron	N/A	NP_001365174.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCG	ENST00000218867.4	TSL:1 MANE Select	c.-1+4002G>C		intron	N/A	ENSP00000218867.3

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39522 AN: 151930 Hom.: 5979 Cov.: 32

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.233

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.260 AC: 39586 AN: 152048 Hom.: 5997 Cov.: 32 AF XY: 0.253 AC XY: 18840 AN XY: 74342

African (AFR) AF: 0.429 AC: 17781 AN: 41404

American (AMR) AF: 0.171 AC: 2616 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 958 AN: 3472

East Asian (EAS) AF: 0.107 AC: 553 AN: 5172

South Asian (SAS) AF: 0.154 AC: 742 AN: 4824

European-Finnish (FIN) AF: 0.160 AC: 1697 AN: 10580

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14404 AN: 67992

Other (OTH) AF: 0.238 AC: 503 AN: 2112

Alfa AF: 0.233 Hom.: 539

Bravo AF: 0.268

Asia WGS AF: 0.180 AC: 626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.91
DANN	Benign	0.68
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7322327; hg19: chr13-23759216;