13-23279524-T-C

Variant names:

• chr13-23279524-T-C
• rs17078558
• NM_000231.3:c.505+46T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000231.3(SGCG):​c.505+46T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,438,842 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SGCG NM_000231.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.498
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCG	NM_000231.3	c.505+46T>C		intron_variant	Intron 5 of 7	ENST00000218867.4	NP_000222.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCG	ENST00000218867.4	c.505+46T>C		intron_variant	Intron 5 of 7	1	NM_000231.3	ENSP00000218867.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1438842 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 716436

African (AFR) AF: 0.00 AC: 0 AN: 32898

American (AMR) AF: 0.00 AC: 0 AN: 44180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25682

East Asian (EAS) AF: 0.00 AC: 0 AN: 39018

South Asian (SAS) AF: 0.00 AC: 0 AN: 84896

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 9.13e-7 AC: 1 AN: 1094920

Other (OTH) AF: 0.00 AC: 0 AN: 59338

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
DANN	Benign	0.61
PhyloP100		-0.50

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: rs17078558; hg19: chr13-23853663;