13-23180605-T-G

Variant names:

• chr13-23180605-T-G
• rs4770402
• NM_001378244.1:c.54+19959T>G

Variant summary

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

The NM_001378244.1(SGCG):​c.54+19959T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 152,118 control chromosomes in the GnomAD database, including 12,010 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 0.39 (12010 hom., cov: 33)
• Consequence: SGCG NM_001378244.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18
• Publications: 3 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, STRONG Submitted by: PanelApp Australia, ClinGen
• autosomal recessive limb-girdle muscular dystrophy type 2C

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

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_001378244.1		c.54+19959T>G		intron	N/A	NP_001365173.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58831 AN: 152000 Hom.: 11998 Cov.: 33

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.387 AC: 58882 AN: 152118 Hom.: 12010 Cov.: 33 AF XY: 0.384 AC XY: 28526 AN XY: 74352

African (AFR) AF: 0.263 AC: 10902 AN: 41510

American (AMR) AF: 0.350 AC: 5356 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1657 AN: 3470

East Asian (EAS) AF: 0.460 AC: 2383 AN: 5182

South Asian (SAS) AF: 0.384 AC: 1852 AN: 4820

European-Finnish (FIN) AF: 0.402 AC: 4250 AN: 10560

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31043 AN: 67972

Other (OTH) AF: 0.387 AC: 818 AN: 2114

Alfa AF: 0.439 Hom.: 55648

Bravo AF: 0.377

Asia WGS AF: 0.436 AC: 1515 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.31
DANN	Benign	0.64
PhyloP100		-2.2
PromoterAI		0.00050	Neutral

Splicing

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

Other links and lift over

dbSNP: rs4770402; hg19: chr13-23754744;