13-23187743-C-T

Variant names:

• chr13-23187743-C-T
• rs3794368
• NM_000231.3:c.-1+6668C>T

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+6668C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,142 control chromosomes in the GnomAD database, including 3,015 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 0.19 (3015 hom., cov: 33)
• Consequence: SGCG NM_000231.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.290
• Publications: 9 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCG	NM_000231.3	c.-1+6668C>T		intron_variant	Intron 1 of 7	ENST00000218867.4	NP_000222.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCG	ENST00000218867.4	c.-1+6668C>T		intron_variant	Intron 1 of 7	1	NM_000231.3	ENSP00000218867.3

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29213 AN: 152024 Hom.: 3013 Cov.: 33

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.192 AC: 29239 AN: 152142 Hom.: 3015 Cov.: 33 AF XY: 0.192 AC XY: 14261 AN XY: 74382

African (AFR) AF: 0.256 AC: 10619 AN: 41504

American (AMR) AF: 0.140 AC: 2143 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 559 AN: 3470

East Asian (EAS) AF: 0.306 AC: 1580 AN: 5160

South Asian (SAS) AF: 0.198 AC: 956 AN: 4828

European-Finnish (FIN) AF: 0.175 AC: 1849 AN: 10594

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11041 AN: 67986

Other (OTH) AF: 0.174 AC: 367 AN: 2110

Alfa AF: 0.169 Hom.: 9601

Bravo AF: 0.190

Asia WGS AF: 0.232 AC: 806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.81
DANN	Benign	0.43
PhyloP100		-0.29
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: rs3794368; hg19: chr13-23761882;